| First Author | Kaminski S | Year | 2011 |
| Journal | J Autoimmun | Volume | 37 |
| Issue | 3 | Pages | 198-208 |
| PubMed ID | 21700422 | Mgi Jnum | J:237967 |
| Mgi Id | MGI:5817566 | Doi | 10.1016/j.jaut.2011.05.018 |
| Citation | Kaminski S, et al. (2011) Coronin 1A is an essential regulator of the TGFbeta receptor/SMAD3 signaling pathway in Th17 CD4(+) T cells. J Autoimmun 37(3):198-208 |
| abstractText | Transforming growth factor beta (TGFbeta) plays a central role in maintaining immune homeostasis by regulating the initiation and termination of immune responses and thus preventing the development of autoimmune diseases. In this study, we describe an essential mechanism by which the actin regulatory protein Coronin 1A (Coro1A) ensures the proper response of Th17 CD4(+) T cells to TGFbeta. Coro1A has been established as a key player in T cell survival, migration, activation, and Ca(2+) regulation in naive T cells. We show that mice lacking Coro1a developed less severe experimental autoimmune encephalomyelitis (EAE). Unexpectedly, upon the re-induction of EAE, Coro1a(-/-) mice exhibited enhanced EAE signs that correlated with increased numbers of IL-17 producing CD4(+) cells in the central nervous system (CNS) compared to wild-type mice. In vitro differentiated Coro1a(-/-) Th17 CD4(+) T cells consistently produced more IL-17 than wild-type cells and displayed a Th17/Th1-like phenotype in regard to the expression of the Th1 markers T-bet and IFNgamma. Mechanistically, the Coro1a(-/-) Th17 cell phenotype correlated with a severe defect in TGFbetaR-mediated SMAD3 activation. Taken together, these data provide experimental evidence of a non-redundant role of Coro1A in the regulation of Th17 CD4(+) cell effector functions and, subsequently, in the development of autoimmunity. |
