Exp Mol Med.  2017 Sep;49(9):e375. 10.1038/emm.2017.132.

Casein kinase 2 is a critical determinant of the balance of Th17 and Treg cell differentiation

• Jang SW
• Hwang SS
• Kim HS
• Lee KO
• Kim MK
• Lee W
• Kim K
• Lee GR

• KMID: 2394306
• DOI: http://doi.org/10.1038/emm.2017.132

Abstract

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.

MeSH Terms

Casein Kinase II*
Casein Kinases*
Caseins*
Central Nervous System
Encephalomyelitis, Autoimmune, Experimental
In Vitro Techniques
RNA, Small Interfering
T-Lymphocytes, Regulatory*
Th17 Cells
Casein Kinase II
Casein Kinases
Caseins
RNA, Small Interfering