Th9 cells in the pathogenesis of EAE and multiple sclerosis

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 gamma 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.