Integrin α3 promotes T17 cell polarization and extravasation during autoimmune neuroinflammation.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including T17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in treating autoimmunity, there are currently no therapeutic interventions that specifically block encephalitogenic T17 cell migration. Here, we report integrin α3 as a T17 cell-selective determinant of pathogenicity in experimental autoimmune encephalomyelitis. CNS-infiltrating T17 cells express high integrin α3, and its deletion in CD4 T cells or fate-mapped cells attenuated disease severity. Mechanistically, integrin α3 enhanced the immunological synapse formation to promote the polarization and proliferation of T17 cells. Moreover, the transmigration of T17 cells into the CNS was dependent on integrin α3, and integrin α3 deficiency enhanced the retention of CD4 T cells in the perivascular space of the blood-brain barrier. Integrin α3-dependent interactions continuously maintain T17 cell identity and effector function. The requirement of integrin α3 in T17 cell pathogenicity suggests integrin α3 as a therapeutic target for MS treatment.