IL-9 Controls Central Nervous System Autoimmunity by Suppressing GM-CSF Production

Abstract

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are inflammatory diseases of the central nervous system (CNS) in which T helper (Th) 17 cells play a major role in the disease pathogenesis. Th17 cells that secrete granulocyte-macrophage colony-stimulating factor (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 to wild-type (WT) counterparts. However, the underlying mechanism by which IL-9 suppresses EAE has not been clearly defined. Here we investigated how IL-9 modulates EAE development. By using mice knockout for IL-9 receptor (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 WT DCs. Our results suggest that IL-9 reduces autoimmune neuroinflammation by suppressing GM-CSF production by CD4 + T cells through the modulation of DCs.