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KMID : 0620920170490090004
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Experimental & Molecular Medicine
2017 Volume.49 No. 9 p.4 ~ p.4
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Casein kinase 2 is a critical determinant of the balance of Th17 and Treg cell differentiation
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Jang Sung-Woong
Hwang Soo-Seok
Kim Hyeong-Su
Lee Keoung-Oh
Kim Min-Kyung
Lee Won-Yong
Kim Ki-Wan
Lee Gap-Ryol
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Abstract
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Th17 cells promote inflammatory reactions, whereas regulatory T (Treg) cells inhibit them. Thus, the Th17/Treg cell balance is critically important in inflammatory diseases. However, the molecular mechanisms underlying this balance are unclear. Here, we demonstrate that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA (shRNA)-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation in vitro. Moreover, CX-4945 ameliorated the symptoms of experimental autoimmune encephalomyelitis and reduced Th17 cell infiltration into the central nervous system. Mechanistically, CX-4945 inhibited the IL-6/STAT3 and Akt/mTOR signaling pathways. Thus, CK2 has a crucial role in regulating the Th17/Treg balance.
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KEYWORD
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Lymphocyte differentiation, T-helper 17 cells
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