Integrin α3 promotes T H 17 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 T H 17 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 T H 17 cell migration. Here, we report integrin α3 as a T H 17 cell-selective determinant of pathogenicity in experimental autoimmune encephalomyelitis. CNS-infiltrating T H 17 cells express high integrin α3, and its deletion in CD4 + T cells or Il17a fate-mapped cells attenuated disease severity. Mechanistically, integrin α3 enhanced the immunological synapse formation to promote the polarization and proliferation of T H 17 cells. Moreover, the transmigration of T H 17 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 T H 17 cell identity and effector function. The requirement of integrin α3 in T H 17 cell pathogenicity suggests integrin α3 as a therapeutic target for MS treatment.