CD5 enhances Th17-cell differentiation by regulating IFN-? response and ROR?t localization.

ABSTRACT: Mechanisms that modulate the generation of Th17 cells are incompletely understood. We report that the activation of casein kinase 2 (CK2) by CD5 is essential for the efficient generation of Th17 cells in vitro and in vivo. In our study, the CD5-CK2 signaling pathway enhanced TCR-induced activation of AKT and promoted the differentiation of Th17 cells by two independent mechanisms: inhibition of glycogen synthase kinase 3 (GSK3) and activation of mTOR. Genetic ablation of the CD5-CK2 signaling pathway attenuated TCR-induced AKT activation and consequently increased activity of GSK3 in Th17 cells. This resulted in increased sensitivity of Th17 cells to IFN-?-mediated inhibition. In the absence of CD5-CK2 signaling, we observed decreased activity of S6K and attenuated nuclear translocation of ROR?t (ROR is retinoic acid receptor related orphan receptor). These results reveal a novel and essential function of the CD5-CK2 signaling pathway and GSK3-IFN-? axis in regulating Th-cell differentiation and provide a possible means to dampen Th17-type responses in autoimmune diseases.

SUBMITTER: McGuire DJ 

PROVIDER: S-EPMC3984608 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature