Fas signaling-mediated T_H9 cell differentiation favors bowel inflammation and antitumor functions.

ABSTRACT: Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes T_H9 cell differentiation by activating NF-κB via Ca²⁺-dependent PKC-β activation. In addition, PKC-β also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas^-induced T_H9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing T_H9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated T_H9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high T_H9 cell nu

SUBMITTER: Shen Y 

PROVIDER: S-EPMC6606754 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature