4165 total record number 127 records this year

STAT1 signaling protects self-reactive T cells from control by innate cells during neuroinflammation

Arbelaez, CA;Palle, P;Charaix, J;Bettelli, E;

The transcription factor Signal transducer and activator of transcription 1 (STAT1) plays a critical role in modulating the differentiation of CD4+ T cells producing IL-17 and GM-CSF, which promote the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The protective role of STAT1 in MS and EAE has been largely attributed to its ability to limit pathogenic T helper (Th) cells and promote regulatory T (Treg) cells. Using mice with selective deletion of STAT1 in T cells (STAT1CD4-Cre), we identify a novel mechanism by which STAT1 regulates neuroinflammation independently of Foxp3+ Treg cells. STAT1-deficient effector T cells become the target of NK cell-mediated killing, limiting their capacity to induce EAE. STAT1-deficient T cells promoted their own killing by producing more IL-2 that in return activated NK cells. Elimination of NK cells restored EAE susceptibility in STAT1CD4-Cre mice. Therefore, our study suggests that the STAT1 pathway can be manipulated to limit autoreactive T cells during autoimmunity directed against the central nervous system.