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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2016-09, Vol.113 (36), p.10145-10150
• Main Authors: Ulges, Alexander, Witsch, Esther J., Pramanik, Gautam, Klein, Matthias, Birkner, Katharina, Bühler, Ulrike, Wasser, Beatrice, Luessi, Felix, Stergiou, Natascha, Dietzen, Sarah, Brühl, Till-Julius, Bohn, Toszka, Bündgen, Georg, Kunz, Horst, Waisman, Ari, Schild, Hansjörg, Schmitt, Edgar, Zipp, Frauke, Bopp, Tobias
• Format: Article
• Language: English
• Subjects: Animals; Biological Sciences; Casein Kinase II - deficiency; Casein Kinase II - genetics; Casein Kinase II - immunology; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Forkhead Transcription Factors; Gene Expression Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-17; Mice; Mice, Inbred C57BL; Mice, Transgenic; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Phosphorylation; Receptors, Interleukin; Severity of Illness Index; Signal Transduction; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - immunology; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Th17 Cells - pathology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1523869113

T helper 17 (TH17) cells represent a discrete TH cell subset instrumental in the immune response to extracellular bacteria and fungi. However, TH17 cells are considered to be detrimentally involved in autoimmune diseases like multiple sclerosis (MS). In contrast to TH17 cells, regulatory T (Treg) cells were shown to be pivotal in the maintenance of peripheral tolerance. Thus, the balance between Treg cells and TH17 cells determines the severity of a TH17 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 TH17 cell development and promotes the generation of Treg 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 TH17 cell development and suggest this kinase as a potential therapeutic target to treat TH17 cell-driven autoimmune responses.