Protein kinase 2 (CK2) controls CD4+ T cell effector function in the pathogenesis of colitis. Academic Article uri icon

Overview

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 CD45RBhi-naive CD4+ T cells from CK2αfl/fl controls and CK2αfl/fldLck-Cre mice into Rag1-/- mice. CD4+ T cells from CK2αfl/fldLck-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.

authors

  • Yang, Wei
  • Gibson, Sara A
  • Yan, Zhaoqi
  • Wei, Hairong
  • Tao, Jiahui
  • Sha, Bingdong
  • Qin, Hongwei
  • Benveniste, Etty N

publication date

  • January 27, 2020

Research

keywords

  • CD4-Positive T-Lymphocytes
  • Colitis
  • Disease Susceptibility
  • Protein Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC7382987

Scopus Document Identifier

  • 85078418809

Digital Object Identifier (DOI)

  • 10.1038/s41385-020-0258-x

PubMed ID

  • 31988467

Additional Document Info

volume

  • 13

issue

  • 5