https://orcid.org/0000-0001-7627-4137
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Satoshi Yoshimura, Rodolfo Thome, Shingo Konno, Elisabeth R Mari, Javad Rasouli, Daniel Hwang, Alexandra Boehm, Yanhua Li, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami, IL-9 Controls Central Nervous System Autoimmunity by Suppressing GM-CSF Production, The Journal of Immunology, Volume 204, Issue 3, February 2020, Pages 531–539, https://doi.org/10.4049/jimmunol.1801113
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Abstract
Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are inflammatory diseases of the CNS in which Th17 cells play a major role in the disease pathogenesis. Th17 cells that secrete GM-CSF are pathogenic and drive inflammation of the CNS. IL-9 is a cytokine with pleiotropic functions, and it has been suggested that it controls the pathogenic inflammation mediated by Th17 cells, and IL-9R−/− mice develop more severe EAE compared with wild-type counterparts. However, the underlying mechanism by which IL-9 suppresses EAE has not been clearly defined. In this study, we investigated how IL-9 modulates EAE development. By using mice knockout for IL-9R, we show that more severe EAE in IL-9R−/− mice correlates with increased numbers of GM-CSF+ CD4+ T cells and inflammatory dendritic cells (DCs) in the CNS. Furthermore, DCs from IL-9R−/− mice induced more GM-CSF production by T cells and exacerbated EAE upon adoptive transfer than did wild-type DCs. Our results suggest that IL-9 reduces autoimmune neuroinflammation by suppressing GM-CSF production by CD4+ T cells through the modulation of DCs.
