Protein Kinase CK2 Maintains Reciprocal Balance Between Th17 and Treg Cells in the Pathogenesis of UC

Abstract

Background T helper 17 and regulatory T cells balance have crucial effects on the development of ulcerative colitis (UC). Currently, how to break this balance has not yet been found. Protein kinase CK2 is involved in the pathogenesis of immune-related disorders. However, its effects on the development of UC are obscure. Methods The level of CK2 in the colonic tissues of UC patients was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and immune-histochemistry. Peripheral blood CD4+ T cells were treated with CK2 inhibitor CX4945 or transfected with Csnk2-interfering lentivirus; the mRNA expression and protein levels of inflammatory cytokines were detected by qRT-PCR, enzyme-linked immunosorbent assay, and flow cytometry. Moreover, CX4945 was administered to trinitrobenzene sulfonic acid (TNBS)–induced colitis mice model for determining the function of CK2 on the regulation of intestinal inflammation. Results The CK2 level was markedly increased in inflamed mucosa of UC and highly expressed in CD4+ T cells. Blockade of CK2 by CX4945 inhibited Th17 but promoted regulatory T-cell (Treg) immune responses in CD4+ T cells from patients with UC. Moreover, CK2 blockade alleviated TNBS-induced colitis in mice. Inhibition of CK2 suppressed Th17 but promoted Treg differentiation by decreasing the phosphorylation level of signal transducer and activator of transcription (STAT) 3 and increasing the phosphorylation level of STAT5. The RNA-Seq and co-immunoprecipitation analysis further showed that CK2 could interact with Sirtuin 1 (SIRT1) and downregulate SIRT1 expression, which participated in Th17 inhibition but promoted Treg differentiation. Sirtuin 1 upregulation ameliorated TNBS-induced colitis, whereas SIRT1 blockade aggravated TNBS-induced colitis in mice. Conclusions CK2 have crucial effects on the development of UC by maintaining reciprocal balance between Th17 and Treg cells. Protein kinase CK2 blockade might be considered as a new therapeutic approach for UC treatment.

Sirtuin family in autoimmune diseases

“…In addition, treatment with EX-527 reduced weight loss and colonic inflammation but increased iTreg differentiation (89). Dong et al showed that the protein kinase CK2 downregulated SIRT1 expression, was involved in Th17 inhibition, and promoted Treg differentiation (90). SIRT1 deficiency may inhibit colitis development by inducing Tregs.…”

“…Dong et al. showed that the protein kinase CK2 downregulated SIRT1 expression, was involved in Th17 inhibition, and promoted Treg differentiation ( 90 ). SIRT1 deficiency may inhibit colitis development by inducing Tregs.…”

The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review

“…Further, the expression of CK2 is increased in the inflamed mucosa of ulcerative colitis (UC) patients. It is important for maintaining reciprocal balance between Th17 and Treg cells [ 189 ]. Interestingly, CK2 activity is reduced, along with an increase in reactive oxygen species (ROS) generation, during acute colitis.…”