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The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF
Open accessAbstract
Interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) require exposure to IL-23 to become encephalitogenic, but the mechanism by which IL-23 promotes their pathogenicity is not known. Here we found that IL-23 induced production of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in T(H)17 cells and that GM-CSF had an essential role in their encephalitogenicity. Our findings identify a chief mechanism that underlies the important role of IL-23 in autoimmune diseases. IL-23 induced a positive feedback loop whereby GM-CSF secreted by T(H)17 cells stimulated the production of IL-23 by antigen-presenting cells. Such cross-regulation of IL-23 and GM-CSF explains the similar pattern of resistance to autoimmunity when either of the two cytokines is absent and identifies T(H)17 cells as a crucial source of GM-CSF in autoimmune inflammation.
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“and to promote the production of effector molecules (El-Behi et al., 2011).”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as El-Behi et al., 2011
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Sorted by citations
Items 301–400 of 955
Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression
Beurel, E., Lowell, J. A., & Jope, R. S. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.04.012 · Cited by 65
Tiam1/Rac1 complex controls Il17a transcription and autoimmunity
Kurdi, A. T., Bassil, R., Olah, M., Wu, C., Xiao, S., Taga, M. F., Frangieh, M., Buttrick, T., Orent, W., Bradshaw, E. M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13048 · Cited by 55
Differential roles of resident microglia and infiltrating monocytes in murine CNS autoimmunity
Shemer, A., & Jung, S. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0519-z · Cited by 66
“Furthermore, it has been shown that IL-23 secretion by APC results in GM-CSF production by Th17 cells, which, in turn, forms a positive feedback loop to further enhance IL-23 secretion [104].”
Th17 reprogramming of T cells in systemic juvenile idiopathic arthritis
Henderson, L. A., Hoyt, K. J., Lee, P. Y., Rao, D. A., Jonsson, A. H., Nguyen, J. P., Rutherford, K. D., Julé, A. M., Charbonnier, L., Case, S., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.132508 · Cited by 73
“joints of chronic sJIA patients compared with healthy control blood, including markers associated with pathogenic Th17 cells (CSF2, GM-CSF) (Figure 5F) (62, 63).”
BackgroundMetabolic regulation of inflammasomes in inflammation
Yang, Q., Liu, R., Yu, Q., Bi, Y., & Liu, G. (2019) · Immunology · doi:10.1111/imm.13056 · Cited by 68
van Egmond, M., Vidarsson, G., & Bakema, J. E. (2015) · Immunological Reviews · doi:10.1111/imr.12333 · Cited by 69
“By contrast, TLR3 signaling (via TRIF) suppresses demyelination in EAE (86).”
InfluentialCherrier, M., & Eberl, G. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.02.003 · Cited by 63
“Other cytokines produced by Th17 cells include IL-22, which also activates epithelial cells to produce anti-microbial peptides, and GM-CSF, which induces a positive feedback loop on the differentiation of Th17 cells and the recruitment of myeloid cells [16,17].”
BackgroundDikmen, H. O., Hemmerich, M., Lewen, A., Hollnagel, J., Chausse, B., & Kann, O. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01903-4 · Cited by 69
“has been defined [11, 14, 80, 81], their effects on microglia-mediated neuronal dysfunction are still controversial [41, 82].”
The IL-12 Cytokine and Receptor Family in Graft-vs.-Host Disease
Bastian, D. A., Wu, Y., Betts, B. C., & Yu, X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00988 · Cited by 75
Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation.
Hartwig, T., Zwicky, P., Schreiner, B., Yawalkar, N., Cheng, P., Navarini, A., Dummer, R., Flatz, L., Conrad, C., Schlapbach, C., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.12.012 · Cited by 62
“IL-1b in turn is well established to induce GM-CSF expression in T cells (El-Behi et al., 2011).”
BackgroundPharmacological inhibition of RORγt suppresses the Th17 pathway and alleviates arthritis in vivo
Guendisch, U., Weiss, J., Ecoeur, F., Riker, J., Kaupmann, K., Kallen, J., Hintermann, S., Orain, D., Dawson, J., Billich, A., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188391 · Cited by 62
Malik, S., Want, M. Y., & Awasthi, A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00014 · Cited by 68
“reported that the neutralization of GM-CSF-attenuated tissue inflammation in EAE (69).”
BackgroundIL‐12‐polarized Th1 cells produce GM‐CSF and induce EAE independent of IL‐23
Grifka‐Walk, H. M., Giles, D. A., & Segal, B. M. (2015) · European Journal of Immunology · doi:10.1002/eji.201545800 · Cited by 71
GM-CSF: Master regulator of the T cell-phagocyte interface during inflammation
Ingelfinger, F., De Feo, D., & Becher, B. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101518 · Cited by 61
Luís, J. P., Simões, C. J. V., & Brito, R. M. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031731 · Cited by 74
“Interestingly, IL-1β treatment in Th17 cells is reported to upregulate the production of the granulocyte macrophage colony-stimulating factor (GM-CSF), an important cytokine that induces the activation and migration of myeloid cells to inflammation sites [121].”
BackgroundActivation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation
Li, J., Shi, W., Sun, H., Ji, Y., Chen, Y., Guo, X., Sheng, H., Shu, J., Zhou, L., Cai, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11304-8 · Cited by 64
Zhang, Y., Han, J., Liang, X., Li, Z., Zhang, F., Rasouli, J., Wang, Z., Zhang, G., & Li, X. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.11.013 · Cited by 72
“These results indicated that miR-23b reduced recruitment and infiltration into the CNS of pathological CD4 T cells, specifically Th1 and Th17 cells.(5) That is to say, disease amelioration in miR23b-treated mice depends on the inhibition of encephalitogenic T cell migration.”
ResultSelf-citationGM-CSF as a therapeutic target in autoimmune diseases
Shiomi, A., Usui, T., & Mimori, T. (2016) · Inflammation and Regeneration · doi:10.1186/s41232-016-0014-5 · Cited by 69
“Recent studies suggest that GM-CSF also has many pro-inflammatory functions and plays critical roles in the development of autoimmune and inflammatory diseases [3, 4].”
BackgroundResultInfluentialNew candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis
Hoppmann, N., Graetz, C., Paterka, M., Poisa-Beiro, L., Larochelle, C., Hasan, M., Lill, C. M., Zipp, F., & Siffrin, V. (2015) · Brain · doi:10.1093/brain/awu408 · Cited by 66
“These recent publications underline the importance of GM-CSF producing T cells in multiple sclerosis for T cell pathogenicity, which had been suggested by recent work in EAE (Codarri et al., 2011; El-Behi et al., 2011).”
BackgroundTargeting GM-CSF in inflammatory and autoimmune disorders
Achuthan, A. A., Lee, M.-C., & Hamilton, J. A. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101523 · Cited by 66
Liver fibrosis and CD206+ macrophage accumulation are suppressed by anti-GM-CSF therapy
Tan-Garcia, A., Lai, F., Yeong, J. P.-S., Irac, S. E., Ng, P. Y., Msallam, R., Lim, J. C. T., Wai, L., Tham, C. Y. L., Choo, S. P., et al. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.11.006 · Cited by 63
“For cell surface phenotyping related to in vitro and in vivo GM-CSF blocking experiments, the following antibodies were used: CD3-BV650 (SP34-2), CD5-BV711 (UCHT2), CD14-PE/Cy7 (M5E2), CD14-AF700 (M5E2), CD19-BV650 (SJ25C1), CD20-BV650 (2H7), CD45-V500 (HI30), CD45RA-FITC (5H9), CD123-BUV395 (7G3), CD169-PE (7-239), C…”
InfluentialInnate Immune Modulation by GM-CSF and IL-3 in Health and Disease
Borriello, F., Galdiero, M. R., Varricchi, G., Loffredo, S., Spadaro, G., & Marone, G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040834 · Cited by 77
“, Th17 lymphocytes) can produce GM-CSF [26,27], some groups have reported the STAT5-dependent expression of this cytokine by a specialized subset of T cell [29–31].”
BackgroundGM-CSF but Not IL-17 Is Critical for the Development of Severe Interstitial Lung Disease in SKG Mice
Shiomi, A., Usui, T., Ishikawa, Y., Shimizu, M., Murakami, K., & Mimori, T. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1303255 · Cited by 65
“Recent reports demonstrated that not IL-17A, but GM-CSF was critical for the pathogenesis of Th cells in experimental autoimmune encephalomyelitis, which had been known as a Th17-mediated disease (19, 20).”
BackgroundInhibitory effect of IL-17 on neural stem cell proliferation and neural cell differentiation
Li, Z., Li, K., Zhu, L. D., Kan, Q., Yan, Y., Kumar, P. R., Xu, H., Rostami, A. M., & Zhang, G. (2013) · BMC Immunology · doi:10.1186/1471-2172-14-20 · Cited by 63
“Yan Y, Ding X, Li K, Ciric B, Wu S, Xu H, Gran B, Rostami A, Zhang GX: CNSspecific therapy for ongoing EAE by silencing IL-17 pathway in astrocytes.”
BackgroundInfluentialSelf-citationChewning, J. H., & Weaver, C. T. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401835 · Cited by 62
“The absence of IL-23 signals results in reduced Th17 production of GM-CSF and IL-22, two critical cytokines in Th17-mediated host protection and inflammation (51, 52).”
BackgroundHighly polarized T h17 cells induce EAE via a T ‐bet independent mechanism
Grifka‐Walk, H. M., Lalor, S. J., & Segal, B. M. (2013) · European Journal of Immunology · doi:10.1002/eji.201343723 · Cited by 57
IL‐1 signaling is critical for expansion but not generation of autoreactive GM‐CSF+ Th17 cells
Mufazalov, I. A., Schelmbauer, C., Regen, T., Kuschmann, J., Wanke, F., Gabriel, L. A., Hauptmann, J., Müller, W., Pinteaux, E., Kurschus, F. C., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201694615 · Cited by 59
“Moreover, while the impact of IL-17 itself for EAE pathogenesis is still controversial (Haak et al , 2009; Ishigame et al , 2009), GM-CSF is indispensable for disease development (Codarri et al , 2011; El-Behi et al , 2011).”
InfluentialAdvances in T Helper 17 Cell Biology: Pathogenic Role and Potential Therapy in Multiple Sclerosis
Volpe, E., Battistini, L., & Borsellino, G. (2015) · Mediators of Inflammation · doi:10.1155/2015/475158 · Cited by 64
Miller, N. M., Wang, J., Tan, Y., & Dittel, B. N. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00287 · Cited by 58
“Along with our colleagues, we showed that the critical cytokine produced by both Th1 and Th17 cells for the induction of EAE is GM-CSF (Ponomarev et al., 2007b; El-Behi et al., 2011).”
BackgroundSelf-citationSTAT4 controls GM-CSF production by both Th1 and Th17 cells during EAE
McWilliams, I. L., Rajbhandari, R., Nozell, S. E., Benveniste, E. N., & Harrington, L. E. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0351-3 · Cited by 73
“Recent reports have indicated that GM-CSF is critical for EAE induction and is produced by both Th1 and Th17 subsets [22, 23].”
BackgroundInfluentialAllergies – A T cells perspective in the era beyond the TH1/TH2 paradigm
Berker, M., Frank, L. J., Geßner, A. L., Graßl, N., Holtermann, A., Höppner, S., Kraef, C., Leclaire, M. D., Maier, P., Messerer, D. A. C., et al. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.11.001 · Cited by 67
The Functional Stability of FOXP3 and RORγt in Treg and Th17 and Their Therapeutic Applications
Ren, J., & Li, B. (2016) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2016.10.002 · Cited by 66
Rasouli, J., Casella, G., Yoshimura, S., Zhang, W., Xiao, D., Garifallou, J., Gonzalez, M. V., Wiedeman, A., Kus, A., Mari, E. R., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.aba9953 · Cited by 57
“TH17 cells in the first stimulation expressed little GM-CSF, which could be due to the suppressive effect of TGF- (8).”
BackgroundResultInfluentialSelf-citationMiyamoto, 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
Asahina, R., & Maeda, S. (2016) · Veterinary Dermatology · doi:10.1111/vde.12351 · Cited by 61
“The current understanding of GM-CSF is focused on its pro-inflammatory functions in autoimmune and inflammatory diseases, particularly Th17 associated diseases.(89) The association of GM-CSF in the pathogenesis of AD has been investigated in mice and humans.”
BackgroundLiu, N., Kan, Q., Zhang, X., Xv, Y.-M., Zhang, S., Zhang, G., & Zhu, L. D. (2014) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2014.10.004 · Cited by 56
“In MS and EAE, myelin-reactive T cells were activated in the peripheral immune system and produce high levels of proinflammatory Th1/Th17 cytokines IFN-γ, TNF-α, IL-17 and GM-CSF; they infiltrate into the CNS, and trigger a cascade of immunological reactions that lead to CNS inflammation and myelin damage (El-Behi et…”
Self-citationProtein Kinase C-θ Promotes Th17 Differentiation via Upregulation of Stat3
Kwon, M.-J., Ma, J., Ding, Y., Wang, R., & Sun, Z. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102941 · Cited by 56
“It should be noted that IL-17 is not absolutely required for the development of EAE, but it is able to induce and promote EAE development (7).”
BackgroundMethodInfluentialInnate Immunity Cells and the Neurovascular Unit
Presta, I., Vismara, M. F. M., Novellino, F., Donato, A., Zaffino, P., Scali, E., Pirrone, K. C., Spadea, M. F., Malara, N., & Donato, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123856 · Cited by 61
Walsh, A., Wechalekar, M., Guo, Y., Yin, X., Weedon, H., Proudman, S., Smith, M. D., & Nagpal, S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183928 · Cited by 56
Meningeal mast cell-T cell crosstalk regulates T cell encephalitogenicity
Russi, A. E., Caulfield, M. E., Guo, Y. X., Lucchinetti, C. F., & Brown, M. A. (2016) · Journal of Autoimmunity · doi:10.1016/j.jaut.2016.06.015 · Cited by 55
“Activated within a day of disease induction, mast cells express multiple pro-inflammatory mediators including IL-1β, a cytokine that promotes T cell production of GM-CSF and is essential for EAE development [8,9].”
BackgroundIslet Antigen-Specific Th17 Cells Can Induce TNF-α–Dependent Autoimmune Diabetes
Li, C.-R., Mueller, E. E., & Bradley, L. M. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301742 · Cited by 48
“Abbreviations used in this article: EAE, experimental autoimmune encephalomyelitis; LN, lymph node; PLN, pancreatic lymph node; T1D, type 1 diabetes; WT, wildtype.”
ResultInfluentialGut dysbiosis and multiple sclerosis
Noto, D., & Miyake, S. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108380 · Cited by 65
Immunopathology alters Th17 cell glucocorticoid sensitivity
Banuelos, J., Cao, Y., Shin, S. C., & Lu, N. Z. (2016) · Allergy · doi:10.1111/all.13051 · Cited by 56
“Pathogenic Th17 cells produce more GM-CSF than nonpathogenic Th17 cells (29).”
BackgroundKastirr, I., Maglie, S., Paroni, M., Alfen, J. S., Nizzoli, G., Sugliano, E., Crosti, M., Moro, M., Steckel, B., Steinfelder, S., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400775 · Cited by 57
“and T-bet expression in Th17 cells, but inhibited GM-CSF production (12, 16).”
BackgroundInfluentialSchweingruber, N., Fischer, H. J., Fischer, L., van den Brandt, J., Karabinskaya, A., Labi, V., Villunger, A., Kretzschmar, B., Huppke, P., Simons, M., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1248-4 · Cited by 54
“However, neither IFNγ nor Il-17 alone is essential for the pathogenic potential of effector T cells [12, 16] but rather gM-CSF seems to be a crucial factor in eAe [6, 11, 24].”
BackgroundSmall molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases
Zeng, J., Li, M., Zhao, Q., Chen, M., Zhao, L., Wei, S., Yang, H., Zhao, Y., Wang, A., Shen, J., et al. (2023) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2023.05.009 · Cited by 59
Wang, R., Campbell, S., Amir, M., Mosure, S. A., Bassette, M. A., Eliason, A. D., Sundrud, M. S., Kamenecka, T. M., & Solt, L. A. (2021) · Nature Communications · doi:10.1038/s41467-020-20385-9 · Cited by 58
Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation
Yasuda, K., Kitagawa, Y., Kawakami, R., Isaka, Y., Watanabe, H., Kondoh, G., Kohwi-shigematsu, T., Sakaguchi, S., & Hirota, K. (2019) · Nature Communications · doi:10.1038/s41467-019-08404-w · Cited by 55
Immunoregulatory effect of mast cells influenced by microbes in neurodegenerative diseases
Girolamo, F., Coppola, C., & Ribatti, D. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.06.017 · Cited by 61
Astrocytes to the rescue! Glia limitans astrocytic endfeet control CNS inflammation
Quintana, F. J. (2017) · Journal of Clinical Investigation · doi:10.1172/jci95769 · Cited by 66
“For example, it would be interesting to study whether TNFα and GM-CSF, cytokines known to contribute to disease pathology in MS and other neurologic disorders (16, 17), can also induce tight junction formation at the glia limitans.”
van Nieuwenhuijze, A. E. M., van de Loo, F. A. J., Walgreen, B., Bennink, M. B., Helsen, M. M. A., van den Bersselaar, L., Wicks, I. P., van den Berg, W. B., & Koenders, M. I. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0683-5 · Cited by 50
“IL-6 and IL-23 enhance GM-CSF production by T cells by binding to the respective receptors, creating a positive feedback loop [17].”
BackgroundInfluentialYu, J., Zhou, X.-F., Nakaya, M., Jin, W., Cheng, X.-H., & Sun, S.-C. (2014) · Journal of Immunology · doi:10.4049/jimmunol.1303237 · Cited by 54
“4A), a cytokine known to be crucial for the encephalitogenicity of Th17 cells (21, 22).”
BackgroundAging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice
Li, H., Zhu, L., Wang, R., Xie, L., Ren, J., Ma, S., Zhang, W., Liu, X., Huang, Z., Chen, B., et al. (2021) · Protein & Cell · doi:10.1007/s13238-021-00882-3 · Cited by 53
“Expression of GM-CSF is a mark of pathogenic Th17 cells (Codarri et al., 2011; El-Behi et al., 2011b).”
BackgroundInfluentialOhradanova‐Repic, A., Machacek, C., Charvet, C., Lager, F., Roux, D. L., Platzer, R., Leksa, V., Mitulović, G., Burkard, T. R., Zlabinger, G. J., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00852 · Cited by 53
“In mice, GM-CSF expression is directly confined to the Th17 subset (72, 73).”
BackgroundIL-3 promotes the development of experimental autoimmune encephalitis.
Renner, K., Hellerbrand, S., Hermann, F., Riedhammer, C., Talke, Y., Schiechl, G., Gomez, M., Kutzi, S., Halbritter, D., Goebel, N., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.87157 · Cited by 53
“Acknowledgments This work was supported by grants from the Deutsche Forschungsgemeinschaft to HB and MM (21-98) and Regensburg Center for Interventional Immunology (RCI) to RW, HB, and MM.”
MethodNoster, R., de Koning, H. D., Maier, E., Prelog, M., Lainka, E., & Zielinski, C. E. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.12.1338 · Cited by 53
Gatekeeper role of brain antigen‐presenting CD11c+ cells in neuroinflammation
Paterka, M., Siffrin, V., Voß, J. O., Werr, J., Hoppmann, N., Gollan, R., Belikan, P., Bruttger, J., Birkenstock, J., Jung, S., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201591488 · Cited by 52
“GM-CSF blockade during the priming and effector phase in EAE has been shown to reduce clinical signs of active EAE (Codarri et al , 2011; El-Behi et al , 2011).”
InfluentialRui, Y., Honjo, T., & Chikuma, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315828110 · Cited by 48
“El-Behi M, et al. (2011) The encephalitogenicity of T(H)17 cells is dependent on IL-1and IL-23-induced production of the cytokine GM-CSF.”
BackgroundEffect of puberty on the immune system: Relevance to multiple sclerosis
Ucciferri, C. C., & Dunn, S. E. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.1059083 · Cited by 58
Joint together: The etiology and pathogenesis of ankylosing spondylitis
Xiong, Y., Cai, M., Xu, Y., Dong, P., Chen, H., He, W., & Zhang, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.996103 · Cited by 65
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 57
Trim33 mediates the proinflammatory function of Th17 cells
Tanaka, S., Jiang, Y., Martínez, G., Tanaka, K., Yan, X. S., Kurosaki, T., Kaartinen, V., Feng, X., Tian, Q., Wang, X., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20170779 · Cited by 73
“GM-CSF produced by Th1 and Th17 cells was shown to play an essential role in EAE (Codarri et al., 2011; El-Behi et al., 2011).”
BackgroundImpact of aging immune system on neurodegeneration and potential immunotherapies
Liang, Z., Zhao, Y., Ruan, L., Zhu, L., Jin, K., Zhuge, Q., Su, D., & Zhao, Y. L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.07.006 · Cited by 64
“Increased IL-23p19 expression inmultiple sclerosis lesions and its induction inmicroglia.”
Paré, A., Mailhot, B., Lévesque, S. A., & Lacroix, S. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.07.146 · Cited by 51
Zhou, J., Cai, W., Jin, M., Xu, J., Wang, Y., Xiao, Y., Li, H., Wang, B., Zhang, Y., Han, J., et al. (2015) · Scientific Reports · doi:10.1038/srep13713 · Cited by 50
The Multifaceted Role of Th17 Lymphocytes and Their Associated Cytokines in Cancer
Alizadeh, D., Katsanis, E., & Larmonier, N. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/957878 · Cited by 55
“We provide an overview on the requirements for Th17 development and the direct or indirect impact of Th17 lymphocytes and the cytokines they produce on antitumor responses.”
Wang, X., Ma, C., Wu, J., & Zhu, J. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23233 · Cited by 49
“GM-CSF also stimulates the expression of IL-23 by antigen-presenting cells, such as dendritic cells, establishing a positive feedback loop to amplify the production of GM-CSF by Th17 cells (El-Behi et al., 2011).”
BackgroundThe interplay between T helper cells and brain barriers in the pathogenesis of multiple sclerosis
Angelini, G., Bani, A., Constantin, G., & Rossi, B. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1101379 · Cited by 57
“A higher number of different populations of activated T cells was found in the CNS parenchyma, CSF and blood of MS patients compared to control subjects indicating that these cells have the capacity to cross brain borders (Wallström et al., 2000; Arbour et al., 2003; BrucklacherWaldert et al., 2009; El-Behi et al., 20…”
BackgroundDutta, D., Kundu, M., Mondal, S., Roy, A., Ruehl, S., Hall, D. A., & Pahan, K. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104575 · Cited by 51
The Diversity of Encephalitogenic CD4+ T Cells in Multiple Sclerosis and Its Animal Models
Segal, B. M. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8010120 · Cited by 60
“Consequently, the dogma was revised to portray Th17, as opposed to Th1 cells, as the key encephalitogenic effectors [62,63].”
BackgroundFeo, D. D., Merlini, A., Brambilla, E., Ottoboni, L., Laterza, C., Menon, R., Srinivasan, S., Farina, C., Manteiga, J. M. G., Butti, E., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92387 · Cited by 54
Pierson, E., & Goverman, J. (2017) · JCI Insight · doi:10.1172/jci.insight.92362 · Cited by 51
Chemokine-Driven Migration of Pro-Inflammatory CD4+ T Cells in CNS Autoimmune Disease
Heng, A. H. S., Han, C. W., Abbott, C. A., McColl, S. R., & Comerford, I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.817473 · Cited by 61
Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy
Mansilla, M. J., Presas‐Rodríguez, S., Teniente‐Serra, A., González-Larreategui, Í., Quirant‐Sánchez, B., Fondelli, F., Djedović, N., Iwaszkiewicz‐Grześ, D., Chwojnicki, K., Miljković, D. M., et al. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00618-z · Cited by 64
Noncanonical STAT3 activity sustains pathogenic Th17 proliferation and cytokine response to antigen
Poholek, C. H., Raphael, I., Wu, D., Revu, S. K., Rittenhouse, N., Uche, U. N., Majumder, S., Kane, L., Poholek, A. C., & McGeachy, M. J. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191761 · Cited by 57
Angelou, C. C., Wells, A. C., Vijayaraghavan, J., Dougan, C. E., Lawlor, R. G., Iverson, E., Lazarevic, V., Kimura, M. Y., Peyton, S. R., Minter, L. M., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03125 · Cited by 63
“We noticed that the expression of the cytokine receptors Il1r1 and Il23r, both previously described as essential for the differentiation of pathogenic Th17 cells in EAE (3, 5, 13, 50, 51), was profoundly inhibited in Let-7Tg and derepressed in Lin28Tg pathogenic Th17-polarized cells.”
BackgroundIL ‐17 in neonatal health and disease
Lawrence, S. M., Ruoss, J. L., & Wynn, J. L. (2017) · American Journal of Reproductive Immunology · doi:10.1111/aji.12800 · Cited by 53
Banerjee, D., Zhao, L., Wu, L., Palanichamy, A., Ergün, A., Peng, L., Quigley, C., Hamann, S., Dunstan, R. W., Cullen, P. F., et al. (2015) · Immunology · doi:10.1111/imm.12570 · Cited by 50
Zong, S.-H., Zeng, G.-F., Fang, Y., Peng, J., Tao, Y., Li, K.-K., & Zhao, J.-M. (2014) · Mediators of Inflammation · doi:10.1155/2014/786947 · Cited by 50
Tob1 plays a critical role in the activation of encephalitogenic T cells in CNS autoimmunity
Schulze‐Topphoff, U., Casazza, S., Varrin‐Doyer, M., Pekarek, K. L., Sobel, R. A., Hauser, S. L., Oksenberg, J. R., Zamvil, S. S., & Baranzini, S. E. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20121611 · Cited by 43
“Recent studies highlighted the importance of GM-CSF regulating the encephalitogenicity of Th1 and Th17 cells in EAE (Codarri et al., 2011; El-Behi et al., 2011).”
BackgroundSecretion of mitochondrial DNA via exosomes promotes inflammation in Behçet's syndrome
Konaka, H., Kato, Y., Hirano, T., Tsujimoto, K., Park, J., Koba, T., Aoki, W., Matsuzaki, Y., Taki, M., Koyama, S., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022112573 · Cited by 49
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 63
Piper, C., Zhou, V., KOMOROWSKI, R. A., Szabó, A., Vincent, B. G., Serody, J. S., Alegre, M., Edelson, B. T., Taneja, R., & Drobyski, W. R. (2019) · Blood · doi:10.1182/blood.2019001696 · Cited by 49
Crotti, C., Agape, E., Becciolini, A., Biggioggero, M., & Favalli, E. G. (2019) · Drugs · doi:10.1007/s40265-019-01192-z · Cited by 49
Yoo, S., Kim, M., Kang, M., Kong, J., Kim, K., Lee, S., Hong, B.-K., Jeong, G. H., Lee, J., Shin, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0456-4 · Cited by 59
Brown, M. A., & Weinberg, R. B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00514 · Cited by 52
He, Z., Ma, J., Wang, R., Zhang, J., Huang, Z., Wang, F., Sen, S., Rothenberg, E. V., & Sun, Z. (2017) · Nature Immunology · doi:10.1038/ni.3832 · Cited by 64
Arbelaez, C. A., Glatigny, S., Duhen, R., Eberl, G., Oukka, M., & Bettelli, E. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1403135 · Cited by 51
“Furthermore, consistent with the idea that IL-7 modulates the differentiation of effector T cells, we found that in all Th-polarizing conditions tested, IL-7 promotes GM-CSF production, a cytokine that has been implicated in the pathogenicity of T cells during EAE (9, 10).”
Califano, D., Sweeney, K. J., Le, H., VanValkenburgh, J., Yager, E. J., O’Connor, W., Kennedy, J. S., Jones, D. M., & Avram, D. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70103 · Cited by 51
Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition
Li, Y., Zhai, P., Zheng, Y., Zhang, J., Kellum, J. A., & Peng, Z. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01415 · Cited by 53
“As shown in Figures 5F,G, we found that the concentration of TNFα was much higher in the CLP + Ab group than in the CLP + ISO group, while the concentration of IL-10 was decreased following Csf2 antibody administration.”
BackgroundInfluentialLi, X., Wang, J., Wu, W., Gao, H., Liu, N., Zhan, G., Li, L., Han, L., & Guo, X. Q. (2020) · FEBS Journal · doi:10.1111/febs.15311 · Cited by 54
Duncker, P., Stoolman, J., Huber, A. K., & Segal, B. (2017) · Journal of Immunology · doi:10.4049/jimmunol.1701484 · Cited by 48
“of EAE in otherwise immunocompetent C57BL/6 mice is dependent on GM-CSF expression during the effector phase (8, 9).”
BackgroundDhawan, S., Palma, G. D., Willemze, R., Hilbers, F., Verseijden, C., Luyer, M., Nuding, S., Wehkamp, J., Souwer, Y., de Jong, E. C., et al. (2016) · American Journal of Physiology - Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00114.2016 · Cited by 48
“IL1 is a potent inducer of Th17 cells (6, 9), and in neuroblastoma cells IL1 was reported to induce expression of ChAT (2).”
BackgroundCutting Edge: Suppression of GM-CSF Expression in Murine and Human T Cells by IL-27
Young, A., Linehan, E., Hams, E., Hall, A. O., McClurg, A. E., Johnston, J. A., Hunter, C. A., Fallon, P. G., & Fitzgerald, D. C. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200131 · Cited by 49
“Given the importance of GM-CSF in the pathogenicity of Th1 cells in EAE (8), we examined whether IL-27 suppressed GMCSF expression by Th1 cells.”
InfluentialDai, H., Ciric, B., Zhang, G.-X., & Rostami, A. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.01.005 · Cited by 48
“Given the crucial role of Th17 cells in the development of EAE (Komiyama et al., 2006; El-Behi et al., 2011), suppression of their infiltration into the CNS is likely an important mechanism underlying the beneficial effects of BBI on this disease.”
Self-citationStoye, D., Schubert, C., Goihl, A., Guttek, K., Reinhold, A., Brocke, S., Grüngreiff, K., & Reinhold, D. (2012) · BioMetals · doi:10.1007/s10534-012-9532-z · Cited by 47
“These Th17 cells have been suggested as major contributors to the pathogenesis of autoimmune inflammation (Weaver et al. 2006, 2007; Bettelli et al. 2007; Steinman 2007) although their enecphalitogenicity was shown to be dependent on other pro-inflammatory cytokines (El-Behi et al. 2011).”
BackgroundMalengier‐Devlies, B., Metzemaekers, M., Wouters, C. H., Proost, P., & Matthys, P. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.766620 · Cited by 64
Chiou, H.-Y. C., Lin, M., Hsiao, P., Chen, C., Chiao, S., Lin, T.-Y., Chen, Y., Wu, D.-C., & Lin, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071584 · Cited by 52
Huang, H., Wang, S.-Y., Jiang, T., Fan, R., Zhang, Z., Mu, J., Li, K., Wang, Y., Jin, L., Lin, F., et al. (2018) · Cellular & Molecular Immunology · doi:10.1038/s41423-018-0164-2 · Cited by 47
Protein Kinase CK2 Controls the Fate between Th17 Cell and Regulatory T Cell Differentiation
Gibson, S. A., Yang, W., Yan, Z., Liu, Y., Rowse, A. L., Weinmann, A. S., Qin, H., & Benveniste, E. N. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601912 · Cited by 47
“Furthermore, Th17 cell–derived GM-CSF is critical for disease progression (45, 46).”
Background
Metadata
- Authors
- El-Behi, M., Ciric, B., Dai, H., Yan, Y., Cullimore, M., Safavi, F., Zhang, G.-X., Dittel, B. N., & Rostami, A.
- Affiliations
- Thomas Jefferson University (US)
- Versiti Blood Center of Wisconsin (US)
- Corresponding author
- Rostami, Abdolmohamad
- ORCID
- Venue
- Nature Immunology
- Published
- 2011-04-24
- Volume
- 12
- Issue
- 6
- Pages
- 568-575
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3116521
- OpenAlex
- W2084388036
- Cited by
- 1,071
- References
- 44
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 38 · 2023: 58 · 2022: 62 · 2021: 72 · 2020: 82 · 2019: 71 · 2018: 74 · 2017: 96 · 2016: 82 · 2015: 108 · 2014: 91 · 2013: 80 · 2012: 73
- FWCI
- 37.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Multiple Sclerosis Society
- Mary E. Groff Surgical and Medical Research and Education Charitable Trust
- National Institute of Neurological Disorders and Stroke (R01NS046782)
- 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 › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- Th17 cells, experimental autoimmune encephalomyelitis, IL-23, GM-CSF, interleukin-1, encephalitogenicity, autoimmune disease, antigen-presenting cells, positive feedback loop, T helper cells
- MeSH terms
- Animals, Antibodies, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental, Female, Flow Cytometry, Glycoproteins, Interleukin-1, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, CD4-Positive T-Lymphocytes, Granulocyte-Macrophage Colony-Stimulating Factor, Transforming Growth Factor beta, Mice, Knockout, Th1 Cells, Coculture Techniques, CD11c Antigen, Mice, Interleukin-1beta, Interleukin-23, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells, Myelin-Oligodendrocyte Glycoprotein
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