CD5 enhances Th17-cell differentiation by regulating IFN-γ response and RORγt localization

Academic Article

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-γ-mediated inhibition. In the absence of CD5-CK2 signaling, we observed decreased activity of S6K and attenuated nuclear translocation of RORγt (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-γ axis in regulating Th-cell differentiation and provide a possible means to dampen Th17-type responses in autoimmune diseases. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 2167899
  • Author List

  • Mcguire DJ; Rowse AL; Li H; Peng BJ; Sestero CM; Cashman KS; De Sarno P; Raman C
  • Start Page

  • 1137
  • End Page

  • 1142
  • Volume

  • 44
  • Issue

  • 4