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

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. Autoimmunity: Inflammation in the balance The enzyme casein kinase 2 is a crucial determinant of the balance between cells that promote or inhibit inflammation in autoimmune disease. Conditions caused by autoimmunity, in which the immune system damages rather than protects, include multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease. An imbalance between pro-inflammatory and anti-inflammatory cells has previously been implicated in autoimmunity, but the reason for this imbalance is unclear. Gap Ryol Lee and colleagues at Sogang University in South Korea have found that casein kinase 2 promotes the development of specific cells of the immune system that can upset the balance in favor of damaging inflammation. A drug that inhibits the enzyme limited the damage in a mouse model of nerve inflammation. This indicates the insight has therapeutic potential, which should be investigated.