Deficiency of the G protein G?q ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation.

ABSTRACT: Many G protein-coupled receptors (GPCRs) are reported to be involved in the pathogenesis of multiple sclerosis (MS), and ~40% of all identified GPCRs rely on the G?q/11 G protein family to stimulate inositol lipid signaling. However, the function of G? subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of G?q in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a well-known mouse model of MS. We discovered that compared with wild-type mice, G?q-knockout mice exhibited less severe EAE symptoms, with lower clinical scores, reduced leukocyte infiltration and less extensive demyelination. Moreover, a significantly lower percentage of Th17 cells, one of the key players in MS pathogenesis, was observed in G?q-knockout EAE mice. Studies in vitro demonstrated that deficiency of G?q in CD4+ T cells directly impaired Th17 differentiation. In addition, deficiency of G?q significantly impaired DC-derived IL-6 production, thus inhibiting Th17 differentiation and the G?q-PLC?-PKC and G?q-MAPKs signaling pathways involved in the reduced IL-6 production by DCs. In summary, our data highlighted the critical role of G?q in regulating Th17 differentiation and MS pathogenesis.

SUBMITTER: Lai W 

PROVIDER: S-EPMC5518818 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other