| First Author | Martin BN | Year | 2016 |
| Journal | Nat Immunol | Volume | 17 |
| Issue | 5 | Pages | 583-92 |
| PubMed ID | 26998763 | Mgi Jnum | J:258997 |
| Mgi Id | MGI:6140888 | Doi | 10.1038/ni.3389 |
| Citation | Martin BN, et al. (2016) T cell-intrinsic ASC critically promotes T(H)17-mediated experimental autoimmune encephalomyelitis. Nat Immunol 17(5):583-92 |
| abstractText | Interleukin 1beta (IL-1beta) is critical for the in vivo survival, expansion and effector function of IL-17-producing helper T (T(H)17) cells during autoimmune responses, including experimental autoimmune encephalomyelitis (EAE). However, the spatiotemporal role and cellular source of IL-1beta during EAE pathogenesis are poorly defined. In the present study, we uncovered a T cell-intrinsic inflammasome that drives IL-1beta production during T(H)17-mediated EAE pathogenesis. Activation of T cell antigen receptors induced expression of pro-IL-1beta, whereas ATP stimulation triggered T cell production of IL-1beta via ASC-NLRP3-dependent caspase-8 activation. IL-1R was detected on T(H)17 cells but not on type 1 helper T (T(H)1) cells, and ATP-treated T(H)17 cells showed enhanced survival compared with ATP-treated T(H)1 cells, suggesting autocrine action of T(H)17-derived IL-1beta. Together these data reveal a critical role for IL-1beta produced by a T(H)17 cell-intrinsic ASC-NLRP3-caspase-8 inflammasome during inflammation of the central nervous system. |
