ALBERT

Description: Publication date: Available online 21 July 2016 Source: Cell Reports Author(s): Fang Du, Abhishek V. Garg, Karis Kosar, Saikat Majumder, David G. Kugler, Gerard Hernandez Mir, Maria Maggio, Matthew Henkel, Adam Lacy-Hulbert, Mandy J. McGeachy 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 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 α v on effector Th17 cells and “ex-Th17” cells, and α v β 3 hi RORγt + cells expanded during EAE. Integrin α v β 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. Graphical abstract Teaser Du et al. demonstrate that pro-inflammatory Th17 cells express the receptor integrin αvβ3 on their surface. Using inhibitors and genetically deficient mice, they show that αvβ3 is required for Th17 cells to induce inflammation in the mouse model of multiple sclerosis by promoting migration in the CNS.