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Divergent role of Gs alpha subunit in CD4 T cells on Th subset differentiation and their inflammatory profile

  • Author(s): Goldstone, Jonathan
  • et al.
Abstract

Cyclic AMP both inhibits and promotes T cell functions; however the effects in a particular T helper subset have been difficult to define. We engineered mice with a deletion of the stimulatory G alpha subunit (Gnas-/-) in CD4⁺ T cells. Gnas-/- CD4 T cells have reduced cAMP accumulation, display weak Th17 and Th1 but normal Th2 responses and fail to elicit colitis. Incubation of Gnas-/ - CD4 T cells with cell permeable cAMP analog restored their impaired phenotype via a PKA-dependent influx of Ca²⁺. These findings define an important role for cAMP in the differentiation of certain Th subsets and their subsequent inflammatory functions and raise the possibility that altering cAMP levels in CD4 T cells could provide an immunomodulatory approach for specific Th subsets

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