Department of Life Science, Sogang University, Seoul, Korea.
Exp Mol Med. 2017 Sep 8;49(9):e375. doi: 10.1038/emm.2017.132.
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.
Th17 细胞促进炎症反应，而调节性 T（Treg）细胞则抑制炎症反应。因此，Th17/Treg 细胞平衡在炎症性疾病中至关重要。然而，这种平衡的分子机制尚不清楚。在这里，我们证明酪蛋白激酶 2（CK2）是 Th17/Treg 细胞平衡的关键决定因素。特异性的药理学抑制剂 CX-4945 抑制 CK2 的活性，以及其小发夹 RNA（shRNA）介导的敲低均能抑制 Th17 细胞分化，但反过来又能促进体外 Treg 细胞分化。此外，CX-4945 改善了实验性自身免疫性脑脊髓炎的症状，并减少了 Th17 细胞向中枢神经系统的浸润。从机制上讲，CX-4945 抑制了 IL-6/STAT3 和 Akt/mTOR 信号通路。因此，CK2 在调节 Th17/Treg 平衡中起着至关重要的作用。
