Inflammatory Th17 Cells Express Integrin ?v?3 for Pathogenic Function.

ABSTRACT: 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 ?3 that is IL-23 dependent. Integrin ?3 was not upregulated on all activated T cells; rather, integrin ?3 was upregulated along with its functional partner integrin ?v on effector Th17 cells and "ex-Th17" cells, and ?v?3(hi) ROR?t(+) cells expanded during EAE. Integrin ?v?3 inhibitors ameliorated clinical signs of EAE, and integrin ?3 deficiency on CD4(+) T cells alone was sufficient to block EAE induction. Furthermore, integrin-?3-deficient Th17 cells, but not Th1 cells, were impaired in their ability to induce EAE. Integrin ?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 ?3 is required for Th17 cell-mediated autoimmune CNS inflammation.

SUBMITTER: Du F 

PROVIDER: S-EPMC5627357 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature