Divergent requirement for Gαs and cAMP in the differentiation and inflammatory profile of distinct mouse Th subsets.

ABSTRACT: cAMP, the intracellular signaling molecule produced in response to GPCR signaling, has long been recognized as an immunosuppressive agent that inhibits T cell receptor activation and T cell function. However, recent studies show that cAMP also promotes T cell-mediated immunity. Central to cAMP production downstream of GPCR activation is the trimeric G protein Gs. In order to reconcile the reports of divergent effects of cAMP in T cells and to define the direct effect of cAMP in T cells, we engineered mice in which the stimulatory Gα subunit of Gs (Gαs) could be deleted in T cells using CD4-Cre (Gnas(ΔCD4)). Gnas(ΔCD4) CD4(+) T cells had reduced cAMP accumulation and Ca2(+) influx. In vitro and in vivo, Gnas(ΔCD4) CD4(+) T cells displayed impaired differentiation to specific Th subsets: Th1

SUBMITTER: Li X 

PROVIDER: S-EPMC3287220 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature