Protein Kinase 2 (CK2) is Required for CD4+ T Cell Function in the Pathogenesis of Colitis

Abstract

Abstract Crohn’s disease (CD) is one of the major forms of inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract. CD is associated with aberrant Th1 and Th17 responses accompanied by high levels of IFN-γ and IL-17, respectively. Protein kinase CK2 is a highly conserved serine-threonine kinase that is involved in several signal transduction pathways, including the JAK/STAT, NF-κB, PI3K/Akt/mTOR and Wnt pathways. Inhibition of CK2 kinase activity by small molecule inhibitor (CX-4945) or genetic deletion of CK2α in CD4+ T cells shifts the balance between Th17 and Tregs. However, the function of CK2 in the pathogenesis of colitis is unknown. Here, we demonstrate that CD4+ T cells from CK2αfl/fl dLck-Cre mice failed to induce wasting disease and intestinal inflammation, accompanied by lower levels of inflammatory cytokines and chemokines in the serum, and decreased IL-17A+, IFN-γ+ and IL-17A+/IFN-γ+ CD4+ T cells in the spleen and colon. Furthermore, CK2α controls CD4+ T cell accumulation in the spleen and colon through a cell-intrinsic mechanism. Thus, our data suggest that CK2α contributes to the pathogenesis of colitis, and that inhibition of CK2 kinase activity may be a novel therapeutic treatment for patients with CD.