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


ABSTRACT: 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.

SUBMITTER: Ulges A 

PROVIDER: S-EPMC5018788 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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

Ulges Alexander A   Witsch Esther J EJ   Pramanik Gautam G   Klein Matthias M   Birkner Katharina K   Bühler Ulrike U   Wasser Beatrice B   Luessi Felix F   Stergiou Natascha N   Dietzen Sarah S   Brühl Till-Julius TJ   Bohn Toszka T   Bündgen Georg G   Kunz Horst H   Waisman Ari A   Schild Hansjörg H   Schmitt Edgar E   Zipp Frauke F   Bopp Tobias T  

Proceedings of the National Academy of Sciences of the United States of America 20160823 36


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 pr  ...[more]

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