Protein kinase CK2 governs the molecular decision between encephalitogenic TH17 cell and Treg cell development

T helper 17 (T(H)17) cells represent a discrete TH cell subset instrumental in the immune response to extracellular bacteria and fungi. However, T(H)17 cells are considered to be detrimentally involved in autoimmune diseases like multiple sclerosis (MS). In contrast to T(H)17 cells, regulatory T (T-reg) cells were shown to be pivotal in the maintenance of peripheral tolerance. Thus, the balance between Treg cells and T(H)17 cells determines the severity of a T(H)17 cell-driven disease and therefore is a promising target for treating autoimmune diseases. However, the molecular mechanisms controlling this balance are still unclear. Here, we report that pharmacological inhibition as well as genetic ablation of the protein kinase CK2 (CK2) ameliorates experimental autoimmune encephalomyelitis (EAE) severity and relapse incidence. Furthermore, CK2 inhibition or genetic ablation prevents T(H)17 cell development and promotes the generation of T-reg cells. Molecularly, inhibition of CK2 leads to reduced STAT3 phosphorylation and strongly attenuated expression of the IL-23 receptor, IL-17, and GM-CSF. Thus, these results identify CK2 as a nodal point in T(H)17 cell development and suggest this kinase as a potential therapeutic target to treat T(H)17 cell-driven autoimmune responses.