Protein kinase 2 (CK2) controls CD4+ T cell effector function in the pathogenesis of colitis

Academic Article

Abstract

  • Crohn’s disease (CD), one of the major forms of inflammatory bowel disease (IBD), is characterized by chronic inflammation of the gastrointestinal tract and associated with aberrant CD4 T-helper type 1 (Th1) and Th17 responses. Protein kinase 2 (CK2) is a conserved serine–threonine kinase involved in signal transduction pathways, which regulate immune responses. CK2 promotes Th17 cell differentiation and suppresses the generation of Foxp3 regulatory T cells. The function of CK2 in CD4 T cells during the pathogenesis of CD is unknown. We utilized the T cell-induced colitis model, transferring CD45RB -naive CD4 T cells from CK2α controls and CK2α dLck-Cre mice into Rag1 mice. CD4 T cells from CK2α dLck-Cre mice failed to induce wasting disease and significant intestinal inflammation, which was associated with decreased interleukin-17A-positive (IL-17A ), interferon-γ-positive (IFN-γ ), and double-positive IL-17A IFN-γ CD4 T cells in the spleen and colon. We determined that CK2α regulates CD4 T cell proliferation through a cell-intrinsic manner. CK2α is also important in controlling CD4 T cell responses by regulating NFAT2, which is vital for T cell activation and proliferation. Our findings indicate that CK2α contributes to the pathogenesis of colitis by promoting CD4 T cell proliferation and Th1 and Th17 responses, and that targeting CK2 may be a novel therapeutic treatment for patients with CD. + + + hi + fl/fl fl/fl −/− + fl/fl + + + + + + + +
  • Published In

  • Mucosal Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Yang W; Gibson SA; Yan Z; Wei H; Tao J; Sha B; Qin H; Benveniste EN
  • Start Page

  • 788
  • End Page

  • 798
  • Volume

  • 13
  • Issue

  • 5