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Protein kinase 2 (CK2) controls CD4+T cell effector function in the pathogenesis of colitis
- Source :
- Mucosal immunology; September 2020, Vol. 13 Issue: 5 p788-798, 11p
- Publication Year :
- 2020
-
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/flcontrols 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.
Details
- Language :
- English
- ISSN :
- 19330219 and 19353456
- Volume :
- 13
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Mucosal immunology
- Publication Type :
- Periodical
- Accession number :
- ejs62071549
- Full Text :
- https://doi.org/10.1038/s41385-020-0258-x