Interleukin-23 (IL-23) is required for inflammatory Th17 cell function in experimental autoimmune encephalomyelitis (EAE), and IL-23 blockade reduces the number of effector Th17 cells in the CNS. We report that pro-inflammatory Th17 cells express high integrin β3 that is IL-23 dependent. Integrin β3 was not upregulated on all activated T cells; rather, integrin β3 was upregulated along with its functional partner integrin αv on effector Th17 cells and “ex-Th17” cells, and αvβ3hi RORγt+ cells expanded during EAE. Integrin αvβ3 inhibitors ameliorated clinical signs of EAE, and integrin β3 deficiency on CD4+ T cells alone was sufficient to block EAE induction. Furthermore, integrin-β3-deficient Th17 cells, but not Th1 cells, were impaired in their ability to induce EAE. Integrin β3−/− T cells induced smaller demyelinated lesions and showed reduced spread and accumulation within the CNS, corresponding with impaired extracellular-matrix-mediated migration. Hence, integrin β3 is required for Th17 cell-mediated autoimmune CNS inflammation.
