Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells

McGinley, Aoife M.; Sutton, Caroline E.; Edwards, Sarah C.; Leane, Charlotte M.; DeCourcey, Joseph; Teijeiro, Ana; Hamilton, John A.; Boon, Louis; Djouder, Nabil; Mills, Kingston H.G.

doi:10.1016/j.immuni.2020.01.002

Cited by 251Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyMultiple Sclerosis Research Studies

Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells

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McGinley, Aoife M., Sutton, Caroline E., Edwards, Sarah C., Leane, Charlotte M., DeCourcey, Joseph, Teijeiro, Ana, Hamilton, John A., Boon, Louis +2 more·2020·Immunity

DOI 10.1016/j.immuni.2020.01.002

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Abstract

Interleukin-17A (IL-17A) is a major mediator of tissue inflammation in many autoimmune diseases. Anti-IL-17A is an effective treatment for psoriasis and is showing promise in clinical trials in multiple sclerosis. In this study, we find that IL-17A-defective mice or mice treated with anti-IL-17A at induction of experimental autoimmune encephalomyelitis (EAE) are resistant to disease and have defective priming of IL-17-secreting γδ T (γδT17) cells and Th17 cells. However, T cells from Il17a-/- mice induce EAE in wild-type mice following in vitro culture with autoantigen, IL-1β, and IL-23. Furthermore, treatment with IL-1β or IL-17A at induction of EAE restores disease in Il17a-/- mice. Importantly, mobilization of IL-1β-producing neutrophils and inflammatory monocytes and activation of γδT17 cells is reduced in Il17a-/- mice. Our findings demonstrate that a key function of IL-17A in central nervous system (CNS) autoimmunity is to recruit IL-1β-secreting myeloid cells that prime pathogenic γδT17 and Th17 cells.

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Deficiency of IL-17A or its signalling components results in decreased hepatic accumulation of myeloid cells in models of NASH.
“Deficiency of this cytokine or its signalling components results in decreased hepatic accumulation of myeloid cells in models of NASH (7,52).”
From NKG2D-mediated detection of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis (2023) · cites this paper as [52]

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Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992 · see citing works
The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145 · see citing works
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265 · see citing works
TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605 · cited 1× · see citing works
“The development of Th17 cells from naive CD4+ T cells is directed by IL-6 in combination with transforming growth factor-b (TGF-b) (Bettelli et al., 2006; Mangan et al., 2006), and this process is enhanced by the presence of IL-1b (Veldhoen et al., 2006).”
Background
Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087 · see citing works
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
Coll, R. C., Robertson, A. A. B., Chae, J. J., Higgins, S. C., Muñoz-Planillo, R., Inserra, M. C., Vetter, I., Dungan, L. S., Monks, B. G., Stutz, A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3806 · Cited by 2,849 · see citing works
Self-citation
Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease
Sandborn, W. J., Feagan, B. G., Rutgeerts, P. J., Hanauer, S. B., Colombel, J., Sands, B. E., Lukáš, M., Fedorak, R. N., Lee, S., Bressler, B. L., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215739 · Cited by 2,716 · see citing works
Phenotypic and functional features of human Th17 cells
Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Filì, L., Ferri, S., Frosali, F., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070663 · Cited by 1,861 · see citing works
Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease
Feagan, B. G., Sandborn, W. J., Gasink, C., Jacobstein, D., Lang, Y., Friedman, J. R., BLANK, M. A., Johanns, J., Gao, L.-L., Ye, M., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1602773 · Cited by 1,851 · see citing works
Innate IL-17-producing cells: the sentinels of the immune system
Cua, D. J., & Tato, C. M. (2010) · Nature reviews. Immunology · doi:10.1038/nri2800 · Cited by 1,578 · see citing works
Interleukin-1 and IL-23 Induce Innate IL-17 Production from γδ T Cells, Amplifying Th17 Responses and Autoimmunity
Sutton, C. E., Lalor, S. J., Sweeney, C. M., Brereton, C. F., Lavelle, E. C., & Mills, K. H. G. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.001 · Cited by 1,553 · see citing works
Self-citation
Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial
Hueber, W., Sands, B. E., Lewitzky, S., Vandemeulebroecke, M., Reinisch, W., Higgins, P. D. R., Wehkamp, J., Feagan, B. G., Yao, M. D., Karczewski, M., et al. (2012) · Gut · doi:10.1136/gutjnl-2011-301668 · Cited by 1,547 · see citing works
IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis
Komiyama, Y., Nakae, S., Matsuki, T., Nambu, A., Ishigame, H., Kakuta, S., Sudo, K., & Iwakura, Y. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.1.566 · Cited by 1,536 · see citing works
T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines
Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., Pin, J. J., Garrone, P., Garcia, E., Saeland, S., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2593 · Cited by 1,526 · cited 1× · see citing works
“IL-17A has been shown to drive the production of IL-1b, IL-6, TNF, and granulocyte macrophage-colony stimulating factor (GM-CSF) from fibroblasts (Fossiez et al., 1996) and epithelial cells (Ishigame et al.”
Background
Targeting IL-17 and TH17 cells in chronic inflammation
Miossec, P., & Kolls, J. K. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3794 · Cited by 1,414 · see citing works
Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling
Chung, Y., Chang, S. H., Martínez, G., Yang, X. O., Nurieva, R., Kang, H. S., Ma, L., Watowich, S. S., Jetten, A. M., Tian, Q., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.02.007 · Cited by 1,198 · see citing works
RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation
Codarri, L., Gyülvészi, G., Tosevski, V., Hesske, L., Fontana, A., Magnenat, L., Suter, T., & Becher, B. (2011) · Nature Immunology · doi:10.1038/ni.2027 · Cited by 1,191 · cited 2× · see citing works
“GM-CSF, produced by Th1 and Th17 cells, was also shown to be a key pathogenic cytokine in EAE (Codarri et al., 2011; El-Behi et al., 2011).”
BackgroundMethod
The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo
McGeachy, M. J., Chen, Y., Tato, C. M., Laurence, A., Joyce-Shaikh, B., Blumenschein, W. M., McClanahan, T. K., O'Shea, J. J., & Cua, D. J. (2009) · Nature Immunology · doi:10.1038/ni.1698 · Cited by 1,074 · see citing works
The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF
El-Behi, M., Ciric, B., Dai, H., Yan, Y., Cullimore, M., Safavi, F., Zhang, G.-X., Dittel, B. N., & Rostami, A. (2011) · Nature Immunology · doi:10.1038/ni.2031 · Cited by 1,071 · see citing works
A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis
Sutton, C. E., Brereton, C. F., Keogh, B., Mills, K. H. G., & Lavelle, E. C. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060285 · Cited by 1,009 · see citing works
Self-citation
Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses
Ishigame, H., Kakuta, S., Nagai, T., Kadoki, M., Nambu, A., Komiyama, Y., Fujikado, N., Tanahashi, Y., Akitsu, A., Kotaki, H., et al. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.009 · Cited by 1,004 · cited 1× · see citing works
“, 1996) and epithelial cells (Ishigame et al., 2009), but also from macrophages (Jovanovic et al.”
Background
IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages.
Jovanović, D., Battista, J. A. D., Pelletier, J., Jolicoeur, F. C., He, Y., Zhang, M., Mineau, F., & Martel‐Pelletier, J. (1998) · PubMed · Cited by 973 · see citing works
IL-17 Stimulates the Production and Expression of Proinflammatory Cytokines, IL-β and TNF-α, by Human Macrophages
Jovanović, D., Battista, J. A. D., Martel‐Pelletier, J., Jolicoeur, F. C., He, Y., Zhang, M., Mineau, F., & Pelletier, J. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.7.3513 · Cited by 867 · see citing works
Comparison of Ustekinumab and Etanercept for Moderate-to-Severe Psoriasis
Griffiths, C. E. M., Strober, B. E., van de Kerkhof, P., Ho, V., Fidelus-Gort, R., Yeilding, N. M., Guzzo, C. A., Xia, Y., Zhou, B., Li, S., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0810652 · Cited by 857 · see citing works
Regulation of inflammatory responses by IL-17F
Yang, X. O., Chang, S. H., Park, H., Nurieva, R., Shah, B., Acero, L., Wang, Y.-H., Schluns, K. S., Broaddus, R. R., Zhu, Z., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071978 · Cited by 739 · see citing works
CD27 is a thymic determinant of the balance between interferon-γ- and interleukin 17–producing γδ T cell subsets
Ribot, J. C., deBarros, A., Pang, D. J., Neves, J. F., Peperzak, V., Roberts, S. J., Girardi, M., Borst, J., Hayday, A. C., Pennington, D. J., et al. (2009) · Nature Immunology · doi:10.1038/ni.1717 · Cited by 628 · see citing works
Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study
Segal, B. M., Constantinescu, C. S., Raychaudhuri, A., Kim, L., Fidelus-Gort, R., & Kasper, L. H. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70173-x · Cited by 479 · see citing works
CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system
Mildner, A., Mack, M., Schmidt, H., Brück, W., Djukic, M., Zabel, M. D., Hille, A., Priller, J., & Prinz, M. (2009) · Brain · doi:10.1093/brain/awp144 · Cited by 445 · see citing works
Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease
King, I. L., Dickendesher, T. L., & Segal, B. M. (2009) · Blood · doi:10.1182/blood-2008-07-168575 · Cited by 444 · see citing works
TLR-dependent T cell activation in autoimmunity
Mills, K. H. G. (2011) · Nature reviews. Immunology · doi:10.1038/nri3095 · Cited by 439 · see citing works
Self-citation
Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis
Hofstetter, H. H., Ibrahim, S. M., Koczan, D., Kruse, N., Weishaupt, A., Toyka, K. V., & Gold, R. (2005) · Cellular Immunology · doi:10.1016/j.cellimm.2005.11.002 · Cited by 418 · see citing works
Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma
Gomes, A. L., Teijeiro, A., Burén, S., Tummala, K. S., Yilmaz, M., Waisman, A., Theurillat, J.-P., Perna, C., & Djouder, N. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.020 · Cited by 401 · see citing works
Self-citation
IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice
Haak, S., Croxford, A. L., Kreymborg, K., Heppner, F. L., Pouly, S., Becher, B., & Waisman, A. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35997 · Cited by 398 · see citing works
Induction, function and regulation of IL‐17‐producing T cells
Mills, K. H. G. (2008) · European Journal of Immunology · doi:10.1002/eji.200838535 · Cited by 381 · see citing works
Self-citation
Cutting Edge: Th1 Cells Facilitate the Entry of Th17 Cells to the Central Nervous System during Experimental Autoimmune Encephalomyelitis
O’Connor, R. A., Prendergast, C. T., Sabatos, C. A., Lau, C. W. Z., Leech, M. D., Wraith, D. C., & Anderton, S. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.6.3750 · Cited by 351 · see citing works
Caspase-1–Processed Cytokines IL-1β and IL-18 Promote IL-17 Production by γδ and CD4 T Cells That Mediate Autoimmunity
Lalor, S. J., Dungan, L. S., Sutton, C. E., Basdeo, S. A., Fletcher, J. M., & Mills, K. H. G. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003597 · Cited by 347 · see citing works
Self-citation
Intestinal Interleukin-17 Receptor Signaling Mediates Reciprocal Control of the Gut Microbiota and Autoimmune Inflammation
Kumar, P., Monin, L., Castillo, P., Elsegeiny, W., Horne, W., Eddens, T., Vikram, A., Good, M., Schoenborn, A. A., Bibby, K., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.007 · Cited by 326 · see citing works
Astrocyte-restricted ablation of interleukin-17-induced ACT1-mediated signaling ameliorates autoimmune encephalomyelitis
Kang, Z., Altuntas, C. Z., Gulen, M. F., Liu, C., Giltiay, N., Qin, H., Liu, L., Qian, W., Ransohoff, R. M., Bergmann, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.03.004 · Cited by 297 · see citing works
Requirement of Endogenous Stem Cell Factor and Granulocyte-Colony-Stimulating Factor for IL-17-Mediated Granulopoiesis
Schwarzenberger, P. O., Huang, W., Ye, P., Oliver, P., Manuel, M., Zhang, Z., Bagby, G., Nelson, S., & Kolls, J. K. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.9.4783 · Cited by 276 · see citing works
Neutrophils Mediate Blood–Spinal Cord Barrier Disruption in Demyelinating Neuroinflammatory Diseases
Aubé, B., Lévesque, S. A., Paré, A., Chamma, É., Kébir, H., Gorina, R., Lécuyer, M., Alvarez, J. I., Koninck, Y. D., Engelhardt, B., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400401 · Cited by 229 · see citing works
Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study
Havrdová, E., Belova, A. N., Goloborodko, A., Tisserant, A., Wright, A., Wallstroem, E., Garren, H., Maguire, R. P., & Johns, D. R. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8128-x · Cited by 226 · see citing works
Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells
Kang, Z., Wang, C., Zepp, J., Wu, L., Sun, K., Zhao, J., Chandrasekharan, U., DiCorleto, P. E., Trapp, B. D., Ransohoff, R. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3505 · Cited by 218 · see citing works
Murine CD27 (−) Vγ6 (+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages
Rei, M., Gonçalves‐Sousa, N., Lança, T., Thompson, R. G., Mensurado, S., Balkwill, F. R., Kulbe, H., Pennington, D. J., & Silva‐Santos, B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1403424111 · Cited by 217 · see citing works
Cxcr2 and Cxcl5 regulate the IL-17/G-CSF axis and neutrophil homeostasis in mice
Mei, J., Liu, Y., Dai, N., Hoffmann, C., Hudock, K. M., Zhang, P., Guttentag, S. H., Kolls, J. K., Oliver, P. M., Bushman, F. D., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60588 · Cited by 194 · see citing works
An Alternative Pathway of Imiquimod-Induced Psoriasis-Like Skin Inflammation in the Absence of Interleukin-17 Receptor A Signaling
Malki, K. E., Karbach, S. H., Huppert, J., Zayoud, M., Reißig, S., Schüler, R., Nikolaev, A., Karram, K., Münzel, T. F., Kuhlmann, C. R. W., et al. (2012) · Journal of Investigative Dermatology · doi:10.1038/jid.2012.318 · Cited by 175 · see citing works
T cell–intrinsic ASC critically promotes TH17-mediated experimental autoimmune encephalomyelitis
Martin, B. N., Wang, C., Zhang, C.-J., Kang, Z., Gulen, M. F., Zepp, J. A., Zhao, J., Bian, G., Do, J., Min, B., et al. (2016) · Nature Immunology · doi:10.1038/ni.3389 · Cited by 154 · see citing works
Myeloid cell transmigration across the CNS vasculature triggers IL-1β–driven neuroinflammation during autoimmune encephalomyelitis in mice
Lévesque, S. A., Paré, A., Mailhot, B., Bellver‐Landete, V., Kébir, H., Lécuyer, M., Alvarez, J. I., Prat, A., Vaccari, J. P. D. R., Keane, R. W., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151437 · Cited by 151 · see citing works
Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells
Allen, A. C., Wilk, M. M., Misiak, A., Borkner, L., Murphy, D. M., & Mills, K. H. G. (2018) · Mucosal Immunology · doi:10.1038/s41385-018-0080-x · Cited by 146 · see citing works
Self-citation
A Review of Biologic Therapies Targeting IL-23 and IL-17 for Use in Moderate-to-Severe Plaque Psoriasis
Campa, M., Mansouri, B., Warren, R. B., & Menter, A. (2015) · Dermatology and Therapy · doi:10.1007/s13555-015-0092-3 · Cited by 143 · see citing works
Neutrophils Amplify Autoimmune Central Nervous System Infiltrates by Maturing Local APCs
Steinbach, K., Piédavent, M., Bauer, S., Neumann, F., & Friese, M. A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202613 · Cited by 137 · see citing works
Recruitment of CCR6-Expressing Th17 Cells by CCL 20 Secreted from IL-1β-, TNF-α-, and IL-17A-Stimulated Endometriotic Stromal Cells
Hirata, T., Osuga, Y., Takamura, M., Kodama, A., Hirota, Y., Koga, K., Yoshino, O., Harada, M., Takemura, Y., Yano, T., et al. (2010) · Endocrinology · doi:10.1210/en.2010-0398 · Cited by 119 · see citing works
Inflammasome-Derived IL-1β Regulates the Production of GM-CSF by CD4+ T Cells and γδ T Cells
Lukens, J. R., Barr, M., Chaplin, D., Chi, H., & Kanneganti, T. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103308 · Cited by 117 · see citing works
Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells
Ronchi, F., Basso, C., Preite, S., Reboldi, A., Baumjohann, D., Perlini, L., Lanzavecchia, A., & Sallusto, F. (2016) · Nature Communications · doi:10.1038/ncomms11541 · Cited by 115 · see citing works
Th17 cell based vaccines in mucosal immunity
Kumar, P., Chen, K., & Kolls, J. K. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.03.011 · Cited by 100 · see citing works
Requirement of IL-17RA in Con A Induced Hepatitis and Negative Regulation of IL-17 Production in Mouse T Cells
Nagata, T., McKinley, L., Peschon, J. J., Alcorn, J. F., Aujla, S. J., & Kolls, J. K. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.11.7473 · Cited by 98 · see citing works
Prolonged, granulocyte–macrophage colony-stimulating factor-dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha
Parsonage, G. N., Filer, A. D., Bik, M., Hardie, D. L., Lax, S., Howlett, K. A., Church, L. D., Raza, K., Wong, S. H., Trebilcock, E., et al. (2008) · Arthritis Research & Therapy · doi:10.1186/ar2406 · Cited by 90 · see citing works
Innate IFN‐γ promotes development of experimental autoimmune encephalomyelitis: A role for NK cells and M1 macrophages
Dungan, L. S., McGuinness, N., Boon, L., Lynch, M. A., & Mills, K. H. G. (2014) · European Journal of Immunology · doi:10.1002/eji.201444612 · Cited by 88 · see citing works
Self-citation
IL‐23 drives differentiation of peripheral γδ17 T cells from adult bone marrow‐derived precursors
Papotto, P. H., Gonçalves‐Sousa, N., Schmolka, N., Iseppon, A., Mensurado, S., Stockinger, B., Ribot, J. C., & Silva‐Santos, B. (2017) · EMBO Reports · doi:10.15252/embr.201744200 · Cited by 71 · see citing works
Therapeutic potential of targeting IL-17
Jones, S. A., Sutton, C. E., Cua, D., & Mills, K. H. G. (2012) · Nature Immunology · doi:10.1038/ni.2450 · Cited by 55 · see citing works
Self-citation
Culturing Mouse Peritoneal Mesothelial Cells
Bot, J., Whitaker, D., Vivian, J. B., Lake, R., Yao, V., & McCauley, R. (2003) · Pathology - Research and Practice · doi:10.1078/0344-0338-00427 · Cited by 45 · see citing works

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Mangan, P.R., Harrington, L.E., O'Quinn, D.B., Helms, W.S., Bullard, D.C., Elson, C.O., Hatton, R.D., Wahl, S.M., Schoeb, T.R., and Weaver, C.T. (2006). Transforming growth factorb induces development of the T(H)17 lineage. Nature 441 , 231-234. http://refhub.elsevier.com/S1074-7613(2030029-7/sref36)

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Self-citation
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γδ T cells: origin and fate, subsets, diseases and immunotherapy
Hu, Y., Hu, Q., Li, Y., Lu, L., Xiang, Z., Yin, Z., Kabelitz, D., & Wu, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01653-8 · Cited by 395 · see citing works
NLRP3 inflammasome in neuroinflammation and central nervous system diseases
Xu, W. R., Huang, Y., & Zhou, R. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01275-w · Cited by 309 · see citing works
“IL-17A can recruit myeloid cells that secrete IL-1 β into the CNS, thereby inducing pathogenic γδ T17 and Th17 cells and in ﬂ uencing the progression of EAE [85].”
TH17 cell heterogeneity and its role in tissue inflammation
Schnell, A., Littman, D. R., & Kuchroo, V. K. (2023) · Nature Immunology · doi:10.1038/s41590-022-01387-9 · Cited by 286 · see citing works
Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity
Schnell, A., Huang, L., Singer, M., Singaraju, A., Barilla, R. M., Regan, B. M. L., Bollhagen, A., Thakore, P. I., Dionne, D., Delorey, T. M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.11.018 · Cited by 268 · see citing works
Itaconate confers tolerance to late NLRP3 inflammasome activation
Bambousková, M., Potůčková, L., Paulenda, T., Kerndl, M., Mogilenko, D. A., Lizotte, K., Swain, A., Hayes, S., Sheldon, R. D., Kim, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108756 · Cited by 246 · see citing works
“Irg1−/− mice had higher proportions of IL-17A-producing T cell receptor delta-expressing (TCRδ+) T cells in the ear, which are known to depend on IL-1β release by myeloid cells (Coll et al., 2015; McGinley et al., 2020).”
Background
Maternal inflammation and its ramifications on fetal neurodevelopment
Kwon, H., Choi, G. B., & Huh, J. R. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.01.007 · Cited by 199 · see citing works
m 6 A demethylase ALKBH5 controls CD4 + T cell pathogenicity and promotes autoimmunity
Zhou, J., Zhang, X., Hu, J., Qu, R., Yu, Z., Xu, H. Y., Chen, H., Yan, L., Ding, C., Zou, Q., et al. (2021) · Science Advances · doi:10.1126/sciadv.abg0470 · Cited by 190 · see citing works
The Cytokine IL-17A Limits Th17 Pathogenicity via a Negative Feedback Loop Driven by Autocrine Induction of IL-24
Chong, W. P., Mattapallil, M. J., Raychaudhuri, K., Bing, S. J., Wu, S., Zhong, Y., Wang, W., Chen, Z., Silver, P. B., Jittayasothorn, Y., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.06.022 · Cited by 183 · see citing works
“Observations implicating other cytokines in the pathogenic effect of Th17 cells had also been reported in the model of experimental autoimmune encephalomyelitis (EAE) (Codarri et al., 2011; El-Behi et al., 2011; Haak et al., 2009; McGinley et al., 2020).”
Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming
Aso, K., Kono, M., Kanda, M., Kudo, Y., Sakiyama, K., Hisada, R., Karino, K., Ueda, Y., Nakazawa, D., Fujieda, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36594-x · Cited by 141 · see citing works
IL-17 in the Pathogenesis of Disease: Good Intentions Gone Awry
Majumder, S., & McGeachy, M. J. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101819-092536 · Cited by 131 · see citing works
Global lactylome reveals lactylation-dependent mechanisms underlying T H 17 differentiation in experimental autoimmune uveitis
Fan, W., Wang, X., Zeng, S., Li, N., Wang, G., Li, R., He, S., Li, W., Huang, J., Li, X., et al. (2023) · Science Advances · doi:10.1126/sciadv.adh4655 · Cited by 122 · see citing works
“…into subtypes with different functions is important in immune defense, but dysregulation of this process can induce multiple inflammatory and autoimmune diseases, including autoimmune uveitis ( 1 , 2 ), systemic lupus ery-thematosus ( 3 ), multiple sclerosis ( 4 ), and Crohn ’ s disease ( 5 ).”
Gut microbiome-mediated regulation of neuroinflammation
Bostick, J. W., Schonhoff, A. M., & Mazmanian, S. K. (2022) · Current Opinion in Immunology · doi:10.1016/j.coi.2022.102177 · Cited by 118 · see citing works
Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines
Hajjar, R., González, E., Fragoso, G., Oliero, M., Alaoui, A. A., Calvé, A., Rendos, H. V., Djediai, S., Cuisiniere, T., Laplante, P., et al. (2022) · Gut · doi:10.1136/gutjnl-2022-328389 · Cited by 120 · see citing works
Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease
Yan, Z., Yang, W., Wei, H., Dean, M. N., Standaert, D. G., Cutter, G., Benveniste, E. N., & Qin, H. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000001036 · Cited by 110 · see citing works
“CNS and cause autoimmune disease.(31) IL-17 also causes neuronal damage,(32) and this finding was recently confirmed using a human autologous iPSC-based model.”
Background
Th17 cells and inflammation in neurological disorders: Possible mechanisms of action
Shi, Y., Wei, B., Li, L., Wang, B., & Sun, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.932152 · Cited by 108 · see citing works
IL-17 mediates protective immunity against nasal infection with Bordetella pertussis by mobilizing neutrophils, especially Siglec-F+ neutrophils
Borkner, L., Curham, L. M., Wilk, M. M., Moran, B., & Mills, K. H. G. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00407-5 · Cited by 101 · see citing works
Self-citation
Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)
Bondt, M. D., Hellings, N., Opdenakker, G., & Struyf, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124558 · Cited by 100 · see citing works
“The differentiation from naive CD4+ T cells into proinflammatory Th17 cells is stimulated by several cytokines, including IL-1β, which also induces secretion of IL-17A from these Th17 cells [98].”
Background
Interleukin-17 affects synaptic plasticity and cognition in an experimental model of multiple sclerosis
Filippo, M. D., Mancini, A., Bellingacci, L., Gaetani, L., Mazzocchetti, P., Zelante, T., Barbera, L. L., LUCA, A. D., Tantucci, M., Tozzi, A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110094 · Cited by 93 · see citing works
Inhibition of the IL-17A axis in adipocytes suppresses diet-induced obesity and metabolic disorders in mice
Teijeiro, A., Garrido, A., Ferré, A., Perna, C., & Djouder, N. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00371-1 · Cited by 91 · see citing works
Self-citation
Engineered probiotics with sustained release of interleukin-2 for the treatment of inflammatory bowel disease after oral delivery
Li, M., Liu, N., Zhu, J., Wu, Y., Niu, L., Liu, Y., Chen, L., Bai, B., Miao, Y., Yang, Y., et al. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122584 · Cited by 91 · see citing works
Cytokines and transcription factors in the differentiation of CD4+ T helper cell subsets and induction of tissue inflammation and autoimmunity
Pawlak, M., Ho, A. W., & Kuchroo, V. K. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.09.001 · Cited by 89 · see citing works
Dermatophyte infection: from fungal pathogenicity to host immune responses
Deng, R., Wang, X., & Li, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1285887 · Cited by 86 · see citing works
Targeting lymphoid-derived IL-17 signaling to delay skin aging
Solá, P., Mereu, E., Bonjoch, J., Casado-Peláez, M., Prats, N., Aguilera, M., Reina, Ó., Blanco, E., Esteller, M., Croce, L. D., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00431-z · Cited by 86 · see citing works
The Role of Gamma-Delta T Cells in Diseases of the Central Nervous System
Wo, J., Zhang, F., Li, Z., Sun, C., Zhang, W.-C., & Sun, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580304 · Cited by 80 · see citing works
“recently demonstrated that IL-17 might recruit IL-1b-secreting myeloid cells that prime pathogenic gd T cells in CNS inflammation (52).”
Background
Dietary ellagic acid therapy for CNS autoimmunity: Targeting on Alloprevotella rava and propionate metabolism
Han, B., Shi, L., Bao, M.-Y., Yu, F.-L., Zhang, Y., Lu, X., Wang, Y., Lin, J., Lin, J.-C., Jia, W., et al. (2024) · Microbiome · doi:10.1186/s40168-024-01819-8 · Cited by 79 · see citing works
“T helper 17 (Th17) cells could contribute to central nervous system (CNS) inflammation development in MS patients by recruiting other immune cells through the production of inflammatory factors [4].”
Background
Th17 cell pathogenicity in autoimmune disease
Park, E., & Ciofani, M. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01535-9 · Cited by 75 · see citing works
Macrophages: From Simple Phagocyte to an Integrative Regulatory Cell for Inflammation and Tissue Regeneration—A Review of the Literature
Mamilos, A., Winter, L., Schmitt, V. H., Barsch, F., Grevenstein, D., Wagner, W. L., Babel, M., Keller, K., Schmitt, C., Gürtler, F., et al. (2023) · Cells · doi:10.3390/cells12020276 · Cited by 71 · see citing works
Cancer-associated fibroblasts promote the migration and invasion of gastric cancer cells via activating IL-17a/JAK2/STAT3 signaling
Zhang, J., Li, S., Zhao, Y., Ma, P., Cao, Y., Liu, C., Zhang, X., Wang, W., Chen, L., & Yin, L. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-4843 · Cited by 65 · see citing works
The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis
Miyamoto, K., Sujino, T., Harada, Y., Ashida, H., Yoshimatsu, Y., Yonemoto, Y., Nemoto, Y., Tomura, M., Melhem, H., Niess, J. H., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113005 · Cited by 64 · see citing works
T reg cell–intrinsic requirements for ST2 signaling in health and neuroinflammation
Hemmers, S., Schizas, M., & Rudensky, A. Y. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20201234 · Cited by 61 · see citing works
“This early response promotes the generation of pathogenic Th17 cells and is blunted in the absence of γδT cells (McGinley et al., 2020; Petermann et al., 2010).”
Background
IL-17: Balancing Protective Immunity and Pathogenesis
Sun, L., Wang, L., Moore, B. B., Zhang, S., Xiao, P., Decker, A. M., & Wang, H. (2023) · Journal of Immunology Research · doi:10.1155/2023/3360310 · Cited by 60 · see citing works
Colony stimulating factors in the nervous system
Chiţu, V., Biundo, F., & Stanley, E. R. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101511 · Cited by 55 · see citing works
Dexmedetomidine alleviates cognitive impairment by reducing blood-brain barrier interruption and neuroinflammation via regulating Th1/Th2/Th17 polarization in an experimental sepsis model of mice
Tian, M., Wang, W., Wang, K., Jin, P., Lenahan, C., Wang, Y., Tan, J., Wen, H., Deng, S., Zhao, F., et al. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108332 · Cited by 53 · see citing works
A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity
Alexander, M., Upadhyay, V., Rock, R., Ramirez, L., Trepka, K. R., Puchalska, P., Orellana, D. A., Ang, Q. Y., Whitty, C., Turnbaugh, J. A., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114891 · Cited by 48 · see citing works
Modulation of p38 MAPK and Nrf2/HO-1/NLRP3 inflammasome signaling and pyroptosis outline the anti-neuroinflammatory and remyelinating characters of Clemastine in EAE rat model
Motawi, T. K., El‐Maraghy, S. A., Kamel, A. S. E. D., Said, S. E., & Kortam, M. A. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115435 · Cited by 48 · see citing works
Host-derived mannose glycans trigger a pathogenic γδ T cell/IL-17a axis in autoimmunity
Alves, I., Santos‐Pereira, B., de la Cruz, N., Campar, A., Pinto, V., Rodrigues, P. M., Araújo, M., Santos, S., Ramos‐Soriano, J., Vasconcelos, C., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abo1930 · Cited by 47 · see citing works
Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt
Cai, W., Chen, X., Men, X., Ruan, H., Hu, M., Liu, S., Lü, T., Liao, J., Zhang, B., Lu, D., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe4827 · Cited by 44 · see citing works
“Subsequently, mRNA level of multiple established IL-17A–associated molecules was up-regulated, including Il12a, Il22, Ifn, and Tnf (24).”
BackgroundInfluential
IL-17 in type II diabetes mellitus (T2DM) immunopathogenesis and complications; molecular approaches
Elahi, R., Nazari, M., Mohammadi, V., Esmaeilzadeh, K., & Esmaeilzadeh, A. (2024) · Molecular Immunology · doi:10.1016/j.molimm.2024.03.009 · Cited by 47 · see citing works
Rhythmic IL-17 production by γδ T cells maintains adipose de novo lipogenesis
Douglas, A., Stevens, B., Rendas, M. A., Kane, H., Lynch, E., Kunkemoeller, B. H., Wessendorf-Rodriguez, K. A., Day, E. A., Sutton, C. E., Brennan, M., et al. (2024) · Nature · doi:10.1038/s41586-024-08131-3 · Cited by 45 · see citing works
“We found that a three-week HFD, before the onset of obesity, enhanced EAE and disrupted the circadian rhythm of IL-17A, leading to constantly elevated levels over 24 h (ref.”
InfluentialSelf-citation
Microglial Nox2 Plays a Key Role in the Pathogenesis of Experimental Autoimmune Encephalomyelitis
Hu, C.-F., Wu, S., Lin, G., Shieh, C.-C. K., Hsu, C.-S., Chen, J.-W., Chen, S., Hong, J., & Chen, S.-J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.638381 · Cited by 45 · see citing works
NKG2D-mediated detection of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis
Marinović, S., Lenartić, M., Mladenić, K., Šestan, M., Kavazović, I., Benić, A., Krapić, M., Rindlisbacher, L., Cokarić Brdovčak, M., Sparano, C., et al. (2023) · Science Immunology · doi:10.1126/sciimmunol.add1599 · Cited by 43 · see citing works
Sex differences regulate immune responses in experimental autoimmune encephalomyelitis and multiple sclerosis
Ryan, L., & Mills, K. H. G. (2021) · European Journal of Immunology · doi:10.1002/eji.202149589 · Cited by 43 · see citing works
Self-citation
Helminth Imprinting of Hematopoietic Stem Cells Sustains Anti-Inflammatory Trained Innate Immunity That Attenuates Autoimmune Disease
Cunningham, K. T., Finlay, C. M., & Mills, K. H. G. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2001225 · Cited by 42 · see citing works
Self-citation
Pharmacological Inhibition of STAT3 by Stattic Ameliorates Clinical Symptoms and Reduces Autoinflammation in Myeloid, Lymphoid, and Neuronal Tissue Compartments in Relapsing–Remitting Model of Experimental Autoimmune Encephalomyelitis in SJL/J Mice
Alhazzani, K., Ahmad, S. F., Al-Harbi, N. O., Attia, S. M., Bakheet, S. A., Sarawi, W. S., Alqarni, S. A., Algahtani, M., & Nadeem, A. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13070925 · Cited by 42 · see citing works
“Elevated STAT3 levels may be associated with increased expression/release of pro-inflammatory cytokines, as well as other mediators, which include IL-1β, iNOS, MPO, and MMP [9,12].”
BackgroundResultInfluential
Influenza vaccine combined with moderate-dose PD1 blockade reduces amyloid-β accumulation and improves cognition in APP/PS1 mice
Xing, Z., Zuo, Z., Hu, D., Zheng, X., Wang, X., Yuan, L., Zhou, L., Qi, F., & Yao, Z. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.09.015 · Cited by 38 · see citing works
JAK1 signaling in dendritic cells promotes peripheral tolerance in autoimmunity through PD-L1-mediated regulatory T cell induction
Vogel, A., Martin, K., Soukup, K., Halfmann, A., Kerndl, M., Brunner, J. S., Hofmann, M., Oberbichler, L., Korosec, A., Kuttke, M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110420 · Cited by 40 · see citing works
Neutrophils, Cancer and Thrombosis: The New Bermuda Triangle in Cancer Research
Langiu, M., Palacios-Acedo, A.-L., Crescence, L., Mège, D., Dubois, C., & Panicot‐Dubois, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031257 · Cited by 39 · see citing works
miRNAs Alter T Helper 17 Cell Fate in the Pathogenesis of Autoimmune Diseases
Huang, J., Xu, X., & Yang, J. Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.593473 · Cited by 38 · see citing works
“Indeed, IL-23p19 mice, IL-17A mice, and mice treated with anti-IL-17A are resistant to the induction of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS (72, 73).”
Background
Evolved to protect, designed to destroy: IL‐17‐producing γδ T cells in infection, inflammation, and cancer
Agerholm, R., & Bekiaris, V. (2021) · European Journal of Immunology · doi:10.1002/eji.202049119 · Cited by 35 · see citing works
IL ‐17 signaling induces iNOS + microglia activation in retinal vascular diseases
Zhou, T., Liu, Y., Yang, Z., Ni, B., Zhu, X., Huang, Z., Xu, H., Feng, Q., Lin, X., He, C., et al. (2021) · Glia · doi:10.1002/glia.24063 · Cited by 37 · see citing works
“The IL-17 could activate many inflammatory cells and stimulate the production of numerous inflammatory cytokines and chemokines, amplifying the inflammatory responses (McGinley et al., 2020; Noueihed et al., 2021; Reed et al., 2020).”
Background
Th17 Cells, Glucocorticoid Resistance, and Depression
Khantakova, J. N., Mutovina, A., Ayriyants, K. A., & Bondar, N. P. (2023) · Cells · doi:10.3390/cells12232749 · Cited by 37 · see citing works
“Thus, although some Th17 lymphocytes may stop producing IL-17, IL-17 still has a pathogenic role in certain autoimmune diseases, either as an effector cytokine or in the priming of Th17 cells [54].”
Background
Therapeutic potential of targeting IL-17 and its receptor signaling in neuroinflammation
Gautam, A. S., & Singh, R. K. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103517 · Cited by 34 · see citing works
Targeting Th17 cells: a promising strategy to treat oral mucosal inflammatory diseases
Wang, Y., Xue, N., Wang, Z., Zeng, X. Y., Ji, N., & Chen, Q. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1236856 · Cited by 32 · see citing works
Riboflavin alleviates fluoride-induced ferroptosis by IL-17A-independent system Xc−/GPX4 pathway and iron metabolism in testicular Leydig cells
Li, X., Yang, J., Shi, E., Lu, Y., Song, X., Luo, H., Wang, J., Liang, C., & Zhang, J. (2024) · Environmental Pollution · doi:10.1016/j.envpol.2024.123332 · Cited by 32 · see citing works
Mild-to-severe traumatic brain injury in children: altered cytokines reflect severity
Ryan, E., Kelly, L. A., Stacey, C., Huggard, D., Duff, E., McCollum, D., Leonard, A., Boran, G. P., Doherty, D. R., Bolger, T., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02390-5 · Cited by 32 · see citing works
Pathogenic Role of Adipose Tissue-Derived Mesenchymal Stem Cells in Obesity and Obesity-Related Inflammatory Diseases
Pestel, J., Blangero, F., & Eljaafari, A. (2023) · Cells · doi:10.3390/cells12030348 · Cited by 31 · see citing works
Differential regulation of microglial states by colony stimulating factors
Stanley, E. R., Biundo, F., Gökhan, Ş., & Chiţu, V. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1275935 · Cited by 30 · see citing works
The role of metabolism in Th17 cell differentiation and autoimmune diseases
Wang, G., Su, Z., Li, H. J., Xiao, L., Li, C., & Lian, G. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108450 · Cited by 29 · see citing works
Group IVE cytosolic phospholipase A 2 limits psoriatic inflammation by mobilizing the anti‐inflammatory lipid N ‐acylethanolamine
Liang, L., Takamiya, R., Miki, Y., Heike, K., Taketomi, Y., Sugimoto, N., Yamaguchi, M., Shitara, H., Nishito, Y., Kobayashi, T., et al. (2022) · The FASEB Journal · doi:10.1096/fj.202101958r · Cited by 30 · see citing works
Lysophosphatidylcholine facilitates the pathogenesis of psoriasis through activating keratinocytes and T cells differentiation via glycolysis
Liu, P., Zhou, Y., Chen, C., Yan, B., Li, L., Zhu, W., Li, J., Chen, M., Su, J., Kuang, Y., et al. (2023) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.19088 · Cited by 29 · see citing works
“IL1β, together with IL- 6 and IL23, is a key cytokine that induces Th17 differentiation.(34) Therefore, the infiltration of Th17 cells in skin lesions of psoriasislike dermatitis treated with LPC might be due to the increased secretion of IL1β in KCs.”
Background
Nalfurafine reduces neuroinflammation and drives remyelination in models of CNS demyelinating disease
Denny, L., Abadey, A. A., Robichon, K., Templeton, N., Prisinzano, T. E., Kivell, B. M., & Flamme, A. C. L. (2021) · Clinical & Translational Immunology · doi:10.1002/cti2.1234 · Cited by 29 · see citing works
From the Genetics of Ankylosing Spondylitis to New Biology and Drug Target Discovery
Zaarour, N., Li, Y., Hui, S., Paul, B., & Chen, L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.624632 · Cited by 29 · see citing works
“The recruitment of IL-1β-producing myeloid cells has been shown to be a key factor driving the IL-17 secretion by γδ T and CD4 cells in the central nervous system (66).”
Background
Rifaximin Prevents T-Lymphocytes and Macrophages Infiltration in Cerebellum and Restores Motor Incoordination in Rats with Mild Liver Damage
Balzano, T., Leone, P., Mincheva, G., Castro, M. C., Reyes, L., Ramón, C., Malaguarnera, M., Llansola, M., & Felipo, V. (2021) · Biomedicines · doi:10.3390/biomedicines9081002 · Cited by 29 · see citing works
“Once infiltrated, CD4 lymphocytes and macrophages contribute to promoting neuroinflammation and activation of microglia [42,57].”
Background
Transcriptomic profiling of pemphigus lesion infiltrating mononuclear cells reveals a distinct local immune microenvironment and novel lncRNA regulators
Huang, Z., Qu, P., Wang, K., Zheng, J., Pan, M., & Zhu, H. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03387-7 · Cited by 29 · see citing works
“IL-1 is a strong inducer of innate IL-17 who in turn, recruits IL-1-secreting myeloid cells [26], suggesting that a positive feedback cycle may exist in pemphigus.”
Background
GPR43 stimulation on TCRαβ+ intraepithelial colonic lymphocytes inhibits the recruitment of encephalitogenic T-cells into the central nervous system and attenuates the development of autoimmunity
Prado, C. E., Espinoza, A., Martínez, E., Petrosino, J. F., Riquelme, E. M., Martín, A. J. M., & Pacheco, R. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02815-9 · Cited by 31 · see citing works
“Nevertheless, many other immune actors play significant roles in this CNS autoimmunity, including local components such as microglia and astrocytes [8–10] and peripheral immune cells infiltrating the CNS, including B-cells [11], monocytes/macrophages [12] and neutrophils [13] among others.”
Background
Impact of type 2 diabetes mellitus on the immunoregulatory characteristics of adipose tissue-derived mesenchymal stem cells
Abu-Shahba, N., Mahmoud, M., El-Erian, A. M., Husseiny, M. I., Eldeen, G. N., Helwa, I., Amr, K. S., ElHefnawi, M., Othman, A. I., Ibrahim, S., et al. (2021) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2021.106072 · Cited by 31 · see citing works
Identification and Clinical Validation of Key Extracellular Proteins as the Potential Biomarkers in Relapsing-Remitting Multiple Sclerosis
Li, M., Chen, H., Yin, P., Song, J., Jiang, F., Tang, Z., Fan, X., Chen, X., Wang, Y.-J., Xue, Y., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.753929 · Cited by 28 · see citing works
Proinflammatory IL-17 levels in serum/cerebrospinal fluid of patients with neurodegenerative diseases: a meta-analysis study
Gautam, A. S., Pulivarthi, C. B., & Singh, R. K. (2022) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-022-02357-6 · Cited by 28 · see citing works
Bystander activation of Bordetella pertussis ‐induced nasal tissue‐resident memory CD4 T cells confers heterologous immunity to Klebsiella pneumoniae
Curham, L. M., Mannion, J. M., Daly, C. M., Wilk, M. M., Borkner, L., Lalor, S. J., McLoughlin, R. M., & Mills, K. H. G. (2023) · European Journal of Immunology · doi:10.1002/eji.202250247 · Cited by 28 · see citing works
Self-citation
Neuroinflammation in Autoimmune Disease and Primary Brain Tumors: The Quest for Striking the Right Balance
Mitchell, D. K., Shireman, J. M., Potchanant, E. A. S., Lara-Velazquez, M. A., & Dey, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.716947 · Cited by 27 · see citing works
Lipidomic profiling reveals metabolic signatures in psoriatic skin lesions
Liu, P., Hou, G., Kuang, Y., Li, L., Chen, C., Yan, B., Zhu, W., Li, J., Chen, M., Su, J., et al. (2022) · Clinical Immunology · doi:10.1016/j.clim.2022.109212 · Cited by 27 · see citing works
Exploring the association and causal effect between white blood cells and psoriasis using large-scale population data
Zhou, G., Ren, X., Tang, Z., Li, W., Chen, W., He, Y., Wei, B., Zhang, H., Ma, F., Chen, X., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1043380 · Cited by 27 · see citing works
“Immune cells derived from monocytes, such as dendritic cells and macrophages, play a crucial role in psoriasis-like inflammation (68, 69) These immune cells can secrete drivers of inflammation, such as IL-23, to promote the incidence of psoriasis (70).”
Background
The Helminth Parasite Heligmosomoides polygyrus Attenuates EAE in an IL-4Rα-Dependent Manner
White, M. P. J., Johnston, C. J. C., Grainger, J. R., Konkel, J. E., O’Connor, R. A., Anderton, S. M., & Maizels, R. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01830 · Cited by 26 · see citing works
“In addition, IL-17A is also thought to recruit activated neutrophils and monocytes into the CNS, facilitating further damage and demyelination which exacerbates symptoms of EAE disease further (46).”
Background
JAK inhibition ameliorated experimental autoimmune encephalomyelitis by blocking GM-CSF-driven inflammatory signature of monocytes
Shao, S., Chen, C., Shi, G.-N., Zhou, Y., Wei, Y.-Z., Wu, L., Sun, L., & Zhang, T.-T. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.07.026 · Cited by 23 · see citing works
Dopaminergic Receptor Targeting in Multiple Sclerosis: Is There Therapeutic Potential?
Melnikov, M., Pashenkov, M. V., & Boyко, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105313 · Cited by 24 · see citing works
Endothelial cell‐derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis
Ruiz, F., Peter, B., Rebeaud, J., Vigne, S., Bressoud, V., Roumain, M., Wyss, T., Yersin, Y., Wagner, I., Kreutzfeldt, M., et al. (2023) · EMBO Reports · doi:10.15252/embr.202255328 · Cited by 22 · see citing works
Mechanisms underlying the beneficial effects of physical exercise on multiple sclerosis: focus on immune cells
Zong, B., Yu, F., Zhang, X., Zhao, W., Li, S., & Li, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1260663 · Cited by 23 · see citing works
REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model
Wang, S., Kozai, M., Mita, H., Cai, Z., Masum, M. A., Ichii, O., Takada, K., & Inaba, M. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112283 · Cited by 22 · see citing works
Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy
Qiu, Y., Peng, Y.-P., Fang, X., Xu, F.-F., Liu, Z., & Cao, B. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.339490 · Cited by 24 · see citing works
Treatment with an antigen-specific dual microparticle system reverses advanced multiple sclerosis in mice
Kwiatkowski, A. J., Helm, E. Y., Stewart, J., Drashansky, T. T., Cho, J. J., Avram, D., & Keselowsky, B. (2022) · bioRxiv · doi:10.1073/pnas.2205417119 · Cited by 21 · see citing works
“6 pathogenic T cells in MS (28, 29), while IL-6 and IL-1β promote Th17 cell differentiation (30).”
Background
PARKIN modifies peripheral immune response and increases neuroinflammation in active experimental autoimmune encephalomyelitis (EAE)
Cossu, D., Yokoyama, K., Sato, S., Noda, S., Sechi, L. A., & Hattori, N. (2021) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2021.577694 · Cited by 23 · see citing works
IL-17A-targeting fenofibrate attenuates inflammation in psoriasis by inducing autophagy
Park, A., & Heo, T. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121755 · Cited by 21 · see citing works
Commensal Microbiome Expands Tγδ17 Cells in the Lung and Promotes Particulate Matter-Induced Acute Neutrophilia
Yang, C., Kwon, D.-I., Kim, M., Im, S., & Lee, Y. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.645741 · Cited by 21 · see citing works
“This is consistent with previous report (49) and we speculate that Tgd17 cells secrete IL-17, which recruits additional neutrophils to the site of inflammation, thus providing more IL-1b by feedforward circuit.”
Result
Systematic analysis of human colorectal cancer scRNA-seq revealed limited pro-tumoral IL-17 production potential in gamma delta T cells
Ran, R., Trapečar, M., & Brubaker, D. K. (2024) · Neoplasia · doi:10.1016/j.neo.2024.101072 · Cited by 20 · see citing works
COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry
Cortellini, A., Gennari, A., Pommeret, F., Patel, G., Newsom-Davis, T. E., Bertuzzi, A. F., Viladot, M., Mirallas, O., Felip, E., Lee, A. J. X., et al. (2022) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djac057 · Cited by 20 · see citing works
Evaluation of the Genetic Diversity, Population Structure and Selection Signatures of Three Native Chinese Pig Populations
Zhong, Z., Wang, Z., Xie, X., Tian, S., Wang, F., Wang, Q., Ni, S., Pan, Y., & Xiao, Q. (2023) · Animals · doi:10.3390/ani13122010 · Cited by 20 · see citing works
“IL-17A promotes the production of corresponding myeloid cells by recruiting pathogenic T cells and plays an initiating role in autoimmunity [37].”
Background
IL-33–Stimulated Murine Mast Cells Polarize Alternatively Activated Macrophages, Which Suppress T Cells That Mediate Experimental Autoimmune Encephalomyelitis
Finlay, C. M., Cunningham, K. T., Doyle, B., & Mills, K. H. G. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901321 · Cited by 20 · see citing works
Self-citation
Can Panax ginseng help control cytokine storm in COVID-19?
Choi, J. H., Lee, Y. H., Kwon, T. W., Ko, S., Nah, S.-Y., & Cho, I. (2022) · Journal of Ginseng Research · doi:10.1016/j.jgr.2022.02.006 · Cited by 20 · see citing works
“Since IL-10 is clearly a gatekeeper of fibrotic/antifibrotic signaling to reduce fibrosis [36], IL-10 may improve acute respiratory distress syndrome [37] or its milder form acute lung injury.”
Fecal microbiota transplantation regulates the microbiota-gut-spinal cord axis to promote recovery after spinal cord injury
Xi, D., Liu, P., Feng, Y., Teng, Y., Liang, Y., Zhou, J., Deng, H., Zeng, G., & Zong, S. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.111212 · Cited by 19 · see citing works
Anti-inflammatory mechanisms and pharmacological actions of phycocyanobilin in a mouse model of experimental autoimmune encephalomyelitis: A therapeutic promise for multiple sclerosis
Marín‐Prida, J., Fuentes, N. P., Lagumersindez-Denis, N., Camacho, H., García-Soca, A. M., Sarduy-Chávez, R. D. L. C., Vieira, É. L. M., Tavares, J. C., Falcón‐Cama, V., Fernández, J. R., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1036200 · Cited by 18 · see citing works
The role of IL-23/IL-17 axis in ischemic stroke from the perspective of gut-brain axis
Jiang, Y., Dai, Y., Liu, Z., Liao, Y., Sun, S., Kong, X., Hu, J., & Tang, Y. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109505 · Cited by 18 · see citing works
Narrow band ultraviolet B therapy deactivates Th1/Th17 pathway and activates Th2 cytokines secretion in Egyptian psoriatic arthritis patients
Farid, A., Tawfik, A., Elsioufy, B., & Safwat, G. (2020) · Journal of Radiation Research and Applied Sciences · doi:10.1080/16878507.2020.1742443 · Cited by 18 · see citing works
Notch3 destabilizes regulatory T cells to drive autoimmune neuroinflammation in multiple sclerosis
Benamar, M., Contini, P., Schmitz‐Abe, K., Lanzetta, O., Getachew, F., Bachelin, C., Leyva-Castillo, J. M., Wang, M., Öktelik, F. B., Perrot, O., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.09.007 · Cited by 17 · see citing works
TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses
Miyashita, Y., Kouwaki, T., Tsukamoto, H., Okamoto, M., Nakamura, K., & Oshiumi, H. (2021) · Life Science Alliance · doi:10.26508/lsa.202101181 · Cited by 17 · see citing works
“IL-17 plays a critical role in the pathogenesis of DTH and autoimmune diseases, such as EAE (Nakae et al, 2002; McGinley et al, 2020).”
Background
Bibliometric Analysis of γδ T Cells as Immune Regulators in Cancer Prognosis
Liu, B., He, X., Wang, Y., Huang, J.-W., Zheng, Y.-B., Li, Y., & Lu, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.874640 · Cited by 17 · see citing works
Aloperine Ameliorates IMQ-Induced Psoriasis by Attenuating Th17 Differentiation and Facilitating Their Conversion to Treg
Zhou, H., Wang, F., Sun, F., Liu, X., Rong, S.-J., Luo, J., Yue, T., Xiao, J., Yang, C., Lu, W.-Y., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.778755 · Cited by 17 · see citing works
Dietary wheat amylase trypsin inhibitors exacerbate CNS inflammation in experimental multiple sclerosis
Zevallos, V. F., Yogev, N., Hauptmann, J., Nikolaev, A., Pickert, G., Heib, V., Fittler, N. J., Steven, S., Luessi, F., Neerukonda, M., et al. (2023) · Gut · doi:10.1136/gutjnl-2023-329562 · Cited by 17 · see citing works
TOX deficiency facilitates the differentiation of IL-17A-producing γδ T cells to drive autoimmune hepatitis
He, Q., Lu, Y., Tian, W., Jiang, R., Yu, W., Liu, Y., Sun, M., Wang, F., Zhang, H., Wu, N., et al. (2022) · Cellular and Molecular Immunology · doi:10.1038/s41423-022-00912-y · Cited by 16 · see citing works

The role of IL-17A in central nervous system autoimmunity
McGinley, A. M. (2017) · Trinity's Access to Research Output (TARA) (Trinity College Dublin)
Self-citation
A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis
Sutton, C. E., Brereton, C. F., Keogh, B., Mills, K. H. G., & Lavelle, E. C. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060285 · Cited by 1,009 · see citing works
Self-citation
IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis
Huber, M., Heink, S., Pagenstecher, A., Reinhard, K., Ritter, J., Visekruna, A., Guralnik, A., Kamradt, T., & Michael, L. (2013) · Frontiers in Immunology · doi:10.3389/conf.fimmu.2013.02.00939 · Cited by 12 · see citing works
Th17 cells, γδ T cells and their interplay in EAE and multiple sclerosis
McGinley, A. M., Edwards, S. C., Raverdeau, M., & Mills, K. H. G. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.01.001 · Cited by 127 · see citing works
Self-citation
ID: 186
Waisman, A., Regen, T., Mufazalov, I. A., & Hauptmann, J. (2015) · Cytokine · doi:10.1016/j.cyto.2015.08.039 · Cited by 1 · see citing works

Authors: McGinley, A. M., Sutton, C. E., Edwards, S. C., Leane, C. M., DeCourcey, J., Teijeiro, A., Hamilton, J. A., Boon, L., Djouder, N., & Mills, K. H. G.
Affiliations: Trinity College Dublin (IE)
Spanish National Cancer Research Centre (ES)
The Royal Melbourne Hospital (AU)
Polpharma Biologics (Netherlands) (NL)
Corresponding author: Mills, Kingston H.G.
ORCID: McGinley, Aoife M.
Edwards, Sarah C.
Leane, Charlotte M.
DeCourcey, Joseph
Teijeiro, Ana
Hamilton, John A.
Boon, Louis
Djouder, Nabil
Mills, Kingston H.G.
Venue: Immunity
Publisher: Elsevier BV
Published: 2020-02
Volume: 52
Issue: 2
Pages: 342-356.e6
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2020.01.002
OpenAlex: W3005175144
Cited by: 248
References: 61
Citations by year: 2026: 27 · 2025: 28 · 2024: 32 · 2023: 57 · 2022: 49 · 2021: 36 · 2020: 19
FWCI: 14.24
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 383 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders: Science Foundation Ireland
Topics: Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords: IL-17A, IL-1β, experimental autoimmune encephalomyelitis, central nervous system autoimmunity, γδT17 cells, Th17 cells, myeloid cells, neutrophils, inflammatory monocytes, IL-23, anti-IL-17A therapy, multiple sclerosis
MeSH terms: Intraepithelial Lymphocytes, Animals, Autoantigens, Central Nervous System, Encephalomyelitis, Autoimmune, Experimental, Mice, Inbred C57BL, Monocytes, Neutrophils, Autoimmunity, Mice, Knockout, Interleukin-17, Myeloid Cells, Mice, Interleukin-1beta, Interleukin-23, Th17 Cells

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Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells

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