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Th9 cells in the pathogenesis of EAE and multiple sclerosis

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Abstract

Interleukin (IL)-9 producing CD4+ T helper cells (Th9) are the newest addition to the T helper cell subsets. IL-9 binds to a heterodimeric receptor consisting of the IL-9 receptor (IL-9R) and a common γ chain also presents in IL-2, IL-4, IL-7, and IL-15 receptor complexes. In addition to Th9 cells, Th17 cells secrete smaller amounts of IL-9. Many functional and regulatory roles associated with Th9 cells are currently not fully understood. IL-9 is a pleiotropic cytokine that affects the activity of multiple cell types in the immune compartment as well as in the central nervous system (CNS). Initially implicated in type 2 inflammation, IL-9 has been recently shown to be a key player in regulating autoimmune responses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Here, we review the current understanding of the role of Th9/IL-9 signaling in EAE and MS. We summarize the source and regulation of Th9 cells in vivo, the influence of IL-9 signaling on peripheral and CNS-resident cells in EAE, and the association between IL-9 and MS disease activity.

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Acknowledgements

We thank Dr. Jaime Imitola for his valuable comments. This work was supported by the Awards from the National Institutes of Health (AI093838 and AI043496 to SJK), the Massachusetts Life Sciences Center (RG110219 to WE), and the National Multiple Sclerosis Society (RG3945 to SJK/WE and PP1734 to WE).

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Authors and Affiliations

  1. Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA

    Wassim Elyaman & Samia J. Khoury

  2. Abu Haidar Neuroscience Institute, American University of Beirut Medical Center, Beirut, Lebanon

    Samia J. Khoury

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  1. Wassim Elyaman
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Correspondence to Wassim Elyaman.

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This article is a contribution to the special issue on Th9 Cells in Immunity and Immunopathological Diseases - Guest Editors: Mark Kaplan and Markus Neurath

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Elyaman, W., Khoury, S.J. Th9 cells in the pathogenesis of EAE and multiple sclerosis. Semin Immunopathol 39, 79–87 (2017). https://doi.org/10.1007/s00281-016-0604-y

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