Inflammatory Th17 Cells Express Integrin α(v)β(3) for Pathogenic Function

Inerleukin-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 β(3) that is IL-23 dependent. Integrin β(3) was not upregulated on all activated T cells; rather, integrin β(3) was upregulated along with its functional partner integrin αv on effector Th17 cells and “ex-Th17” cells, and αvβ(3)(hi) RORγt(+) cells expanded during EAE. Integrin αvβ(3) inhibitors ameliorated clinical signs of EAE, and integrin β(3) deficiency on CD4(+) T cells alone was sufficient to block EAE induction. Furthermore, integrin-β(3)-deficient Th17 cells, but not Th1 cells, were impaired in their ability to induce EAE. Integrin β(3)(−/−) T cells induced smaller demyelinated lesions and showed reduced spread and accumulation within the CNS, corresponding with impaired extracellular-matrix-mediated migration. Hence, integrin β(3) is required for Th17 cell-mediated autoimmune CNS inflammation.