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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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Mosmann, T. R., Cherwinski, H. M., Bond, M. W., Giedlin, M. A., & Coffman, R. L. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.7.2348 · Cited by 7,553
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 · cited 1×
“The initial development of T H 17 cells from naive CD4 + T cells is directed by transforming growth factor-β (TGF-β) in combination with IL-6, IL-21 or IL-9 (refs”
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
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
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
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906
IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells
Korn, T., Bettelli, E., Gao, W., Awasthi, A., Jäger, A., Strom, T. B., Oukka, M., & Kuchroo, V. K. (2007) · Nature · doi:10.1038/nature05970 · Cited by 1,896
McGeachy, M. J., Bak-Jensen, K. S., Chen, Y., Tato, C. M., Blumenschein, W., McClanahan, T., & Cua, D. J. (2007) · Nature Immunology · doi:10.1038/ni1539 · Cited by 1,520
Generation of pathogenic TH17 cells in the absence of TGF-β signalling
Ghoreschi, K., Laurence, A., Yang, X.-P., Tato, C. M., McGeachy, M. J., Konkel, J. E., Ramos, H. L., Wei, L., Davidson, T. S., Bouladoux, N., et al. (2010) · Nature · doi:10.1038/nature09447 · Cited by 1,388
Reboldi, A., Coisne, C., Baumjohann, D., Benvenuto, F., Bottinelli, D., Lira, S., Uccelli, A., Lanzavecchia, A., Engelhardt, B., & Sallusto, F. (2009) · Nature Immunology · doi:10.1038/ni.1716 · Cited by 1,206 · cited 1×
“The CCR6-CCL20 axis is essential for the entry of T H 17 cells into the CNS in the early phase of EA”
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- McGeachy, M.J. et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat. Immunol. 10, 314–324 (2009). · DOI · Paper page
- Park, L.S., Friend, D., Gillis, S. & Urdal, D.L. Characterization of the cell surface receptor for granulocyte-macrophage colony-stimulating factor. J. Biol. Chem. 261, 4177–4183 (1986). · DOI
- Fleetwood, A.J., Lawrence, T., Hamilton, J.A. & Cook, A.D. Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation. J. Immunol. 178, 5245–5252 (2007). · DOI · Paper page
- Hirota, K. et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat. Immunol. 12, 255–263 (2011). · DOI · Paper page
- Yang, X.O. et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORα and RORγ. Immunity 28, 29–39 (2008). · DOI · Paper page
- Yamazaki, T. et al. CCR6 regulates the migration of inflammatory and regulatory T cells. J. Immunol. 181, 8391–8401 (2008). · DOI
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Sorted by citations
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Benmamar-Badel, A., Owens, T., & Wlodarczyk, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00430 · Cited by 124
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García, S., Hartkamp, L. M., Fernandez, B. M., van Es, I. E., Lin, H., Wong, J., Long, L., Zanghi, J. A., Rankin, A. L., Masteller, E. L., et al. (2016) · Arthritis Research & Therapy · doi:10.1186/s13075-016-0973-6 · Cited by 114
“the sustained recruitment of immature monocytes to affected tissues [5–7].”
BackgroundMarking and Quantifying IL-17A-Producing Cells In Vivo
Price, A. E., Reinhardt, R. L., Liang, H.-E., & Locksley, R. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039750 · Cited by 89
“Indeed, recent reports have demonstrated critical contributions by GMCSF rather than IL-17 in the pathogenesis of EAE [50,51].”
BackgroundT-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation
Kwong, B., Rua, R., Gao, Y., Flickinger, J. C., Wang, Y., Kruhlak, M. J., Zhu, J., Vivier, É., McGavern, D. B., & Lazarevic, V. (2017) · Nature Immunology · doi:10.1038/ni.3816 · Cited by 120
Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
Constantinescu, C. S., Asher, A., Fryze, W., Kozubski, W. P., Wagner, F. D., Aram, J., Tănăsescu, R., Korolkiewicz, R. P., Dirnberger‐Hertweck, M., Steidl, S., et al. (2015) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000117 · Cited by 105
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BackgroundCytokine‐regulated Th17 plasticity in human health and diseases
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Leibowitz, S., & Yan, J. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00084 · Cited by 98
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BackgroundSchulze‐Topphoff, U., Shetty, A., Varrin‐Doyer, M., Molnarfi, N., Sagan, S. A., Sobel, R. A., Nelson, P. A., & Zamvil, S. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033797 · Cited by 95
“Recent studies demonstrated the important role of GM-CSF on the encephalitogenicity of Th1 and Th17 cells in EAE [19,20].”
ResultPhysiological and pathophysiological functions of SOCE in the immune system
Patrick, J. S. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/540 · Cited by 71
“It was recently found that granulocyte macrophage colony stimulating factor (GM-CSF) production by Th17 cells is required to induce EAE (49, 50).”
BackgroundInfluentialJang, W. Y., Hwang, J. Y., & Cho, J. Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076119 · Cited by 117
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BackgroundIL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis
Adamopoulos, I. E., Suzuki, É., Chao, C., Gorman, D., Adda, S., Maverakis, E., Zarbalis, K. S., Geissler, R. H., Asio, A., Blumenschein, W. M., et al. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204782 · Cited by 93
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van Nieuwenhuijze, A. E. M., Koenders, M. I., Roeleveld, D. M., Sleeman, M. A., van den Berg, W., & Wicks, I. P. (2013) · Molecular Immunology · doi:10.1016/j.molimm.2013.05.002 · Cited by 87
Brockmann, L., Tran, A., Huang, Y., Edwards, M., Ronda, C., Wang, H. H., & Ivanov, I. I. (2023) · Immunity · doi:10.1016/j.immuni.2023.11.003 · Cited by 115
Paré, A., Mailhot, B., Lévesque, S. A., Juzwik, C., Ignatius Arokia Doss, P. M., Lécuyer, M.-A., Prat, A., Rangachari, M., Fournier, A., & Lacroix, S. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714948115 · Cited by 94
“One reported effect of IL-1β treatment on pathogenic T cells is the increased production of GM-CSF, which correlates with their encephalitogenecity (10, 15, 19).”
BackgroundNovel GM-CSF signals via IFN-γR/IRF-1 and AKT/mTOR license monocytes for suppressor function
Ribechini, E., Hutchinson, J. A., Hergovits, S., Heuer, M., Lucas, J., Schleicher, U., Garrote, A.-L. J., Potter, S. J., Riquelme, P., Brackmann, H., et al. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017006858 · Cited by 101
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BackgroundPlanas, R., Santos, R. G., Ojer, P. T., Cruciani, C., Lutterotti, A., Faigle, W., Schaeren‐Wiemers, N., Espejo, C., Eixarch, H., Pinilla, C., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat4301 · Cited by 115
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Hall, J. A., Pokrovskii, M. V., Kroehling, L., Kim, B., Kim, S. Y., Wu, L., Lee, J., & Littman, D. R. (2020) · Immunity · doi:10.1016/j.immuni.2022.09.013 · Cited by 104
Ishigame, H., Zenewicz, L. A., Sanjabi, S., Licona-Limón, P., Nakayama, M., Leonard, W. J., & Flavell, R. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1304498110 · Cited by 89
“However, the regulation of CD4 T-cell differentiation by TGF-β1 is context dependent, as TGF-β1 has been shown to suppress IL-22 and GM-CSF production from Th17 cells (16, 17), whereas it promotes Th9 cell differentiation in the presence of IL-4 (18, 19).”
BackgroundControversies on the role of Th17 in cancer: a TGF-β-dependent immunosuppressive activity?
Martin, F., Apétoh, L., & Ghiringhelli, F. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.09.007 · Cited by 104
Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective
Zwicky, P., Unger, S., & Becher, B. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20191123 · Cited by 91
An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17 cells
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Slyepchenko, A., Maes, M., Köhler, C. A., Anderson, G., Quevedo, J., Alves, G. S., Berk, M., Fernandes, B. S., & Carvalho, A. F. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.02.002 · Cited by 89
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Hercus, T. R., Dhagat, U., Kan, W. L., Broughton, S. E., Nero, T. L., Perugini, M., Sandow, J. J., D’Andrea, R. J., Ekert, P. G., Hughes, T. P., et al. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.03.002 · Cited by 97
“requirement for the pathogenicity of these cells in encephalomyelitis [36,37].”
BackgroundInfluentialKim, M. J., Kim, K., Park, H. J., Kim, G.-R., Hong, K. H., Oh, J. H., Son, J., Park, D. J., Kim, D., Choi, J.-M., et al. (2023) · Nature Immunology · doi:10.1038/s41590-022-01373-1 · Cited by 90
Franken, A., Mol, P. V., Vanmassenhove, S., Donders, E., Schepers, R., Brussel, T. V., Dooms, C., Yserbyt, J., Crem, N. D., Testelmans, D., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005323 · Cited by 101
Starossom, S. C., Veremeyko, T., Yung, A. W. Y., Dukhinova, M., Au, C., Lau, A. Y. L., Weiner, H. L., & Ponomarev, E. D. (2015) · Circulation Research · doi:10.1161/circresaha.115.306847 · Cited by 90
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Yan, Y., Ding, X., Li, K., Ćirić, B., Wu, S., Xu, H., Gran, B., Rostami, A. M., & Zhang, G. (2012) · Molecular Therapy · doi:10.1038/mt.2012.12 · Cited by 89
Self-citationBălașa, R., Bărcuţean, L., Bălașa, A. F., Moțățăianu, A., Roman-Filip, C., & Manu, D. R. (2020) · Human Immunology · doi:10.1016/j.humimm.2020.02.009 · Cited by 121
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
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Louis, C., Souza-Fonseca-Guimarães, F., Yang, Y., D'Silva, D. B., Kratina, T., Dagley, L., Hediyeh-zadeh, S., Rautela, J., Masters, S., Davis, M., et al. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20191421 · Cited by 87
Self-citationZhan, Y., Lew, A. M., & Chopin, M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02679 · Cited by 89
Cytokine Signaling in Multiple Sclerosis and Its Therapeutic Applications
Palle, P., Monaghan, K. L., Milne, S. M., & Wan, E. C. K. (2017) · Medical Sciences · doi:10.3390/medsci5040023 · Cited by 91
“This was shown by studies demonstrating that IL-23 induces the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) in IL-17 cells, and GM-CSF is the main pathogenic factor of EAE [120,122].”
BackgroundMethodZhang, Y., Li, X., Ćirić, B., Ma, C., Gran, B., Rostami, A. M., & Zhang, G. (2015) · Scientific Reports · doi:10.1038/srep17407 · Cited by 92
Self-citationReynolds, G., Gibbon, J. R., Pratt, A., Wood, M. J., Coady, D., Raftery, G., Lorenzi, A., Gray, A., Filer, A., Buckley, C., et al. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-206578 · Cited by 87
“27 28 GM-CSF is thought to exert its pathogenic effect in this model by enhancing IL-23 production by CNS-in fi ltrating CD11c+ DCs and thereby stabilising the Th17 population.”
BackgroundTh17 cells in central nervous system autoimmunity
Sie, C., Korn, T., & Mitsdoerffer, M. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.03.009 · Cited by 95
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Keely, S., Walker, M. M., Marks, E., & Talley, N. J. (2015) · European Journal of Clinical Investigation · doi:10.1111/eci.12548 · Cited by 96
Jamshidian, A., Shaygannejad, V., Pourazar, A., Zarkesh‐Esfahani, S. H., & Gharagozloo, M. (2013) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2013.06.007 · Cited by 90
Cook, A. D., Pobjoy, J., Sarros, S., Steidl, S., Dürr, M. C., Lacey, D. C., & Hamilton, J. A. (2012) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2012-201703 · Cited by 86
Cho, J. J., Xu, Z., Parthasarathy, U., Drashansky, T. T., Helm, E. Y., Zuniga, A. N., Lorentsen, K. J., Mansouri, S., Cho, J. Y., Edelmann, M. J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08605-3 · Cited by 92
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Lee, P. W., Smith, A. J., Yang, Y., Selhorst, A. J., Liu, Y., Racke, M. K., & Lovett‐Racke, A. E. (2017) · JCI Insight · doi:10.1172/jci.insight.91663 · Cited by 93
“It is also interesting that GM-CSF was expressed in the myelin-specific T cells that were both highly encephalitogenic and nonencephalitogenic, suggesting that, although GM-CSF expression by T cells is necessary to be encephalitogenic (36–39), it is not sufficient.”
BackgroundCao, Y., Amezquita, R. A., Kleinstein, S. H., Stathopoulos, P., Nowak, R. J., & O’Connor, K. C. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1501339 · Cited by 94
“Conversely, T cells producing IL-17 and IL-10 are protective and maintain immune homeostasis (30, 31, 33, 34, 43).”
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T cell mediated pathogenesis in EAE: Molecular mechanisms
Kurschus, F. C. (2015) · Biomedical Journal · doi:10.4103/2319-4170.155590 · Cited by 95
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BackgroundGM-CSF contributes to aortic aneurysms resulting from SMAD3 deficiency
Ye, P., Chen, W., Wu, J., Huang, X., Li, J., Wang, S., Liu, Z., Wang, G., Yang, X. Y., Zhang, P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67356 · Cited by 79
“IL-1 IL-1 β or IFN-γ deficiency has also been shown to significantly induce GM-CSF expression (27, 30, 31), which may explain the disease severity observed in Smad3 +/– Ifng –/– mice.”
Zhan, Y., Xu, Y., & Lew, A. M. (2012) · Molecular Immunology · doi:10.1016/j.molimm.2012.04.009 · Cited by 87
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Couture, A., Garnier, A., Docagne, F., Boyer, O., Vivien, D., Mauff, B. L., Latouche, J., & Toutirais, O. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01081 · Cited by 97
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BackgroundT Cell–Macrophage Interactions and Granuloma Formation in Vasculitis
Hilhorst, M. L., Shirai, T., Berry, G. J., Goronzy, J. J., & Weyand, C. M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00432 · Cited by 84
“More recently, it has been reported that Th17 cells produce GM-CSF when stimulated with IL-23 and that this production is upregulated by IL-1β (114).”
BackgroundStorelli, E., Cassina, N., Rasini, E., Marino, F., & Cosentino, M. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00013 · Cited by 87
Basdeo, S. A., Moran, B., Cluxton, D., Canavan, M., McCormick, J., Connolly, M. C., Orr, C. K., Mills, K. H. G., Veale, D. J., Fearon, U., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402990 · Cited by 92
Hamilton, J. A. (2015) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2015.1024110 · Cited by 94
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BackgroundRosenkranz, E., Maywald, M., Hilgers, R.-D., Brieger, A., Clarner, T., Kipp, M., Plümäkers, B., Meyer, S., Schwerdtle, T., & Rink, L. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.11.010 · Cited by 86
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BackgroundChen, J., Cascio, J. A., Magee, J., Techasintana, P., Gubin, M. M., Dahm, G. M., Calaluce, R., Yu, S., & Atasoy, U. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301188 · Cited by 76
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Baeten, D., & Kuchroo, V. K. (2013) · Nature Medicine · doi:10.1038/nm.3268 · Cited by 75
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Prajeeth, C. K., Löhr, K., Floess, S., Zimmermann, J., Ulrich, R., Gudi, V., Beineke, A., Baumgärtner, W., Müller, M., Huehn, J., et al. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.01.001 · Cited by 76
Identity crisis of Th17 cells: many forms, many functions, many questions
Sundrud, M. S., & Trivigno, C. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.10.021 · Cited by 77
“L-23 promotes expression of the non-canonical Th17 cytokine, M-CSF, and this has been shown to be important in EAE pathoenesis [140,141].”
BackgroundZheng, Y., Wang, Z., Wei, S., Liu, Z., & Chen, G. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.11.034 · Cited by 84
Chyuan, I., & Lai, J. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113928 · Cited by 89
The meninges: new therapeutic targets for multiple sclerosis
Russi, A. E., & Brown, M. A. (2014) · Translational research · doi:10.1016/j.trsl.2014.08.005 · Cited by 90
“GM-CSF is a cytokine that has recently been shown to be necessary and sufficient to confer encephalitogenicity to T cells.(101,102) Furthermore, mast cells cocultured with previously primed myelin-specific T cells induce GM-CSF production by T cells (Walker et al, unpublished observation, 2012).”
BackgroundRegulation and function of innate and adaptive interleukin‐17‐producing cells
Hirota, K., Ahlfors, H., Duarte, J. H., & Stockinger, B. (2011) · EMBO Reports · doi:10.1038/embor.2011.248 · Cited by 75
“This induction recruits other inflammatory cells and enlarges atherosclerotic lesions (Erbel et al , 2009; Smith et al , 2010).”
Th17 cell pathogenicity in autoimmune disease
Park, E., & Ciofani, M. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01535-9 · Cited by 75
“IL-23-mediated Th17 cell pathogenicity is achieved by suppressing IL-10 expression and inducing the expression of GM-CSF and IFN γ 47,48,70,112 .”
Pawlak, M., Ho, A. W., & Kuchroo, V. K. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.09.001 · Cited by 93
Ericksen, R. E., Rose, S. E., Westphalen, C. B., Shibata, W., Muthupalani, S., Tailor, Y. H., Friedman, R. A., Han, W., Fox, J. G., Ferrante, A. W., et al. (2013) · Gut · doi:10.1136/gutjnl-2013-305092 · Cited by 77
Poppensieker, K., Otte, D.-M., Schürmann, B., Limmer, A., Dresing, P., Drews, E., Schumak, B., Klotz, L., Raasch, J., Mildner, A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114153109 · Cited by 75
“Two recent studies demonstrated that T-cell–derived GM-CSF sustained neuroinflammation via myeloid cells that infiltrated the CNS (41, 42).”
ResultNorimoto, A., Hirose, K., Iwata, A., Tamachi, T., Yokota, M., Takahashi, K., Saijo, S., Iwakura, Y., & Nakajima, H. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0522oc · Cited by 76
“Furthermore, freshly isolated MLN CD4(1) T cells from Clec4n mice produced less IL-17A and GM-CSF, recently identified as another effector cytokine produced from Th17 cells (26, 27).”
BackgroundPathogenic function of bystander-activated memory-like CD4+ T cells in autoimmune encephalomyelitis
Lee, H., Lee, J.-U., Kim, D.-H., Lim, S., Kang, I., & Choi, J. (2019) · Nature Communications · doi:10.1038/s41467-019-08482-w · Cited by 86
Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer
Punkenburg, E., Vogler, T., Büttner, M., Amann, K., Waldner, M., Atreya, R. N., Abendroth, B., Mudter, J., Merkel, S., Gallmeier, E., et al. (2015) · Gut · doi:10.1136/gutjnl-2014-308227 · Cited by 73
Chong, W. P., Horai, R., Mattapallil, M. J., Silver, P. B., Chen, J., Zhou, R., Sergeev, Y. V., Villasmil, R., Chan, C., & Caspi, R. R. (2013) · Journal of Autoimmunity · doi:10.1016/j.jaut.2013.08.003 · Cited by 81
“GM-CSF has recently been identified as the shared effector molecule of both Th1 and Th17 effector CD4+ T cells that are responsible for the pathology of EAE [27,28].”
BackgroundThe GM-CSF receptor family: Mechanism of activation and implications for disease
Hercus, T., Broughton, S., Ekert, P., Ramshaw, H., Perugini, M., Grimbaldeston, M., Woodcock, J., Thomas, D., Pitson, S., Hughes, T., et al. (2012) · Growth Factors · doi:10.3109/08977194.2011.649919 · Cited by 73
“…as a hemopoietic CSF (Metcalf 2008), evidence now suggests that GM-CSF plays an important role in signaling emergency myelopoiesis in response to infection and in innate and adaptive immunity (Fleetwood et al. 2005; Shibasaki et al. 2007; Metcalf 2010; Codarri et al. 2011; El-Behi et al. 2011).”
BackgroundTh17 Cells in Periodontitis and Its Regulation by A20
Huang, N., Dong, H., Luo, Y., & Shao, B. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.742925 · Cited by 84
“Particularly, IL-23 in turn promotes GM-CSF production and forms a vicious cycle (112).”
BackgroundFatty acid synthase regulates the pathogenicity of Th17 cells
Marks, K. E., Flaherty, S., Woodman, K., Sharma-Walia, N., & Reynolds, J. M. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ab0417-159rr · Cited by 85
“Although Th17 cells produce IL-17, other reports have demonstrated that Th17-derived IFN-g and GM-CSF are what makes a Th17 cell pathogenic for autoimmune inflammation [21, 22, 32].”
BackgroundCho, J. J., Stewart, J. M., Drashansky, T. T., Brusko, M., Zuniga, A. N., Lorentsen, K. J., Keselowsky, B. G., & Avram, D. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.07.029 · Cited by 84
“Th17 cells are CD4+ T cells that express the lineage transcription factor Rorγt and produce the proinflammatory cytokines IL-17A, IL-17F, and, in the setting of EAE, GM-CSF [10-14], while Th1 cells express the lineage transcription factor T-bet and produce the proinflammatory cytokine IFNγ, and were also demonstrated…”
T-helper cell diversity in experimental autoimmune encephalomyelitis and Multiple Sclerosis
Carbajal, K. S., Mironova, Y. A., Ulrich-Lewis, J. T., Kulkarni, D., Grifka-Walk, H. M., Huber, A. K., Shrager, P., Giger, R., & Segal, B. (2015) · Journal of Immunology · doi:10.4049/jimmunol.1501097 · Cited by 72
Dharra, R., Sharma, A. K., & Datta, S. (2023) · Cytokine · doi:10.1016/j.cyto.2023.156287 · Cited by 82
Larochelle, C., Lécuyer, M., Alvarez, J. I., Charabati, M., Saint‐Laurent, O., Ghannam, S., Kébir, H., Flanagan, K., Yednock, T. A., Duquette, P., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24415 · Cited by 80
Communication between pathogenic T cells and myeloid cells in neuroinflammatory disease
Deak, L. C., Greter, M., & Becher, B. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.09.007 · Cited by 78
A gradient of glucocorticoid sensitivity among helper T cell cytokines
Banuelos, J., & Lu, N. (2016) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2016.05.002 · Cited by 70
“GM-CSF deficient Th17 cells are unable to induce experimental autoimmune encephalomyelitis, highlighting the importance of Th17-derived GM-CSF in driving disease pathology [14, 15].”
BackgroundParticipation of interleukin 17A in neuroimmune interactions
Moynes, D. M., Vanner, S. J., & Lomax, A. E. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.03.004 · Cited by 70
High levels of virus-specific CD4+ T cells predict severe pandemic influenza A virus infection.
Zhao, Y., Zhang, Y.-H., Denney, L., Young, D., Powell, T., Peng, Y.-C., Li, N., Yan, H.-P., Wang, D.-Y., Shu, Y., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201207-1245oc · Cited by 70
IL-17 Silencing Does Not Protect Nonobese Diabetic Mice from Autoimmune Diabetes
Joseph, J., Bittner, S., Kaiser, F. M. P., Wiendl, H., & Kissler, S. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101215 · Cited by 68
“Furthermore, the pathogenicity of Th17 cells in EAE was very recently shown to critically depend on their secretion of GM-CSF (26, 27).”
BackgroundEctonucleotidases in Acute and Chronic Inflammation
Giuliani, A. L., Sarti, A. C., & Virgilio, F. D. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.619458 · Cited by 83
“Pathogenic Th17 cells secrete GM-CSF (El-Behi et al., 2011; Lee et al., 2012), while IL-6and TGF-β-stimulated, non-pathogenic, Th17 cells secrete IL-10 and express NTPDase1/CD39 and NT5E/CD73 (Chalmin et al.”
BackgroundInfluentialTugues, S., Amorim, A., Spath, S., Martin‐Blondel, G., Schreiner, B., Feo, D. D., Lutz, M., Guscetti, F., Apostolova, P., Haftmann, C., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat8410 · Cited by 80
Maintenance of Immune Homeostasis through ILC/T Cell Interactions
von Burg, N., Turchinovich, G., & Finke, D. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00416 · Cited by 69
Th17 cells in autoimmune diseases
Han, L., Yang, J. C., Wang, X., Li, D., Lv, L., & Li, B. (2015) · Frontiers of Medicine · doi:10.1007/s11684-015-0388-9 · Cited by 80
“Encephalitogenic GM-CSF also contributes to the maintenance of the Th17 phenotype [100].”
BackgroundLi, B., Gurung, P., Malireddi, R. K. S., Vogel, P., Kanneganti, T., & Geiger, T. L. (2015) · Nature Communications · doi:10.1038/ncomms7131 · Cited by 65
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 81
“Also, IL-23-activated gd T cells suppress the factor forkhead box P3+ (Foxp3) -expressing Treg cells conversion, as well as promoting effector T (Te) cells response (46, 47).”
BackgroundInfluentialProgress Toward the Elusive Pseudomonas aeruginosa Vaccine
Merakou, C., Schaefers, M., & Priebe, G. P. (2018) · Surgical Infections · doi:10.1089/sur.2018.233 · Cited by 68
Chang, Y., Jia, X., Fang, W., Wang, C., Sun, X., Xu, S., Yang, X., Zhao, Y., Chen, J., Wu, H., et al. (2016) · Scientific Reports · doi:10.1038/srep26239 · Cited by 64
Hatfield, J. K., & Brown, M. A. (2015) · Cellular Immunology · doi:10.1016/j.cellimm.2015.06.006 · Cited by 81
Piper, C. J. M., Pesenacker, A. M., Bending, D., Thirugnanabalan, B., Varsani, H., Wedderburn, L. R., & Nistala, K. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38647 · Cited by 68
“It was therefore unexpected when data from studies of IL-17–deficient mice suggested that IL-17 was redundant for induction of autoimmunity in a mouse model of multiple sclerosis, and that granulocyte–macrophage colony-stimulating factor (GM-CSF) was instead necessary and sufficient for disease (6,7).”
BackgroundResultInfluentialLewis, N. D., Haxhinasto, S. A., Anderson, S. M., Stefanopoulos, D. E., Fogal, S. E., Adusumalli, P., Desai, S. N., Patnaude, L. A., Lukas, S., Ryan, K. R., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201810 · Cited by 69
Mourik, B. C., Lubberts, E., de Steenwinkel, J. E. M., Ottenhoff, T. H. M., & Leenen, P. J. M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00294 · Cited by 68
“, IFN-γ and IL-17, respectively, were found dispensable in EAE and instead GM-CSF appeared to be the effector cytokine responsible for IL-23-induced encephalopathy (118).”
BackgroundInterleukin 10 modulation of pathogenic Th17 cells during fatal alphavirus encephalomyelitis
Kulcsar, K. A., Baxter, V. K., Greene, I. P., & Griffin, D. E. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418966111 · Cited by 73
IFN-γ ameliorates autoimmune encephalomyelitis by limiting myelin lipid peroxidation
Sosa, R. A., Murphey, C. L., Robinson, R. R., & Forsthuber, T. G. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505955112 · Cited by 70
“To test whether NAC treatment affected the frequencies or cytokine differentiation of MOG35–55–specific CD4+ T-cell responses, we performed cytokine ELISPOT assays for IFN-γ, IL-17, GM-CSF, and IL-5.”
BackgroundInfluentialDing, X., Yan, Y.-P., Li, X., Li, K., Ciric, B., Yang, J.-X., Zhang, Y., Wu, S., Xu, H., Chen, W.-J., et al. (2015) · Journal of Immunology · doi:10.4049/jimmunol.1303321 · Cited by 66
“cell development by inhibiting IL-23R expression (13) and production of GM-CSF (14), a cytokine necessary for the encephalitogenicity of both Th1 and Th17 cells (15).”
BackgroundSelf-citationPeelen, E., Damoiseaux, J., Muris, A., Knippenberg, S., Smolders, J., Hupperts, R., & Thewissen, M. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2014.10.008 · Cited by 66
Immunopathogenesis of Neuromyelitis Optica
Levy, M., Wildemann, B., Jarius, S., Arellano, B., Sasidharan, S., Weber, M. S., & Stüve, O. (2014) · Advances in immunology · doi:10.1016/b978-0-12-800100-4.00006-4 · Cited by 61
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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