| First Author | Du F | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 5 | Pages | 1339-1351 |
| PubMed ID | 27452457 | Mgi Jnum | J:238869 |
| Mgi Id | MGI:5824457 | Doi | 10.1016/j.celrep.2016.06.065 |
| Citation | Du F, et al. (2016) Inflammatory Th17 Cells Express Integrin alphavbeta3 for Pathogenic Function. Cell Rep 16(5):1339-51 |
| abstractText | 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 beta3 that is IL-23 dependent. Integrin beta3 was not upregulated on all activated T cells; rather, integrin beta3 was upregulated along with its functional partner integrin alphav on effector Th17 cells and "ex-Th17" cells, and alphavbeta3(hi) RORgammat(+) cells expanded during EAE. Integrin alphavbeta3 inhibitors ameliorated clinical signs of EAE, and integrin beta3 deficiency on CD4(+) T cells alone was sufficient to block EAE induction. Furthermore, integrin-beta3-deficient Th17 cells, but not Th1 cells, were impaired in their ability to induce EAE. Integrin beta3(-/-) T cells induced smaller demyelinated lesions and showed reduced spread and accumulation within the CNS, corresponding with impaired extracellular-matrix-mediated migration. Hence, integrin beta3 is required for Th17 cell-mediated autoimmune CNS inflammation. |
