Protein kinase CK2 governs the molecular decision between encephalitogenic T H 17 cell and T reg cell development

6533b823fe1ef96bd127e12c

RESEARCH PRODUCT

Protein kinase CK2 governs the molecular decision between encephalitogenic T H 17 cell and T reg cell development

Felix Luessi Natascha Stergiou Till-julius Brühl Toszka Bohn Frauke Zipp Tobias Bopp Ari Waisman Ulrike Bühler Hansjörg Schild Matthias Klein Beatrice Wasser Alexander Ulges Edgar Schmitt Georg Bündgen Esther Witsch Katharina Birkner Gautam Pramanik Sarah Dietzen Horst Kunz

subject

STAT3 Transcription Factor 0301 basic medicine Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Cell Mice Transgenic chemical and pharmacologic phenomena Biology Severity of Illness Index T-Lymphocytes Regulatory Mice 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Humans IL-2 receptor Phosphorylation Casein Kinase II STAT3 Multidisciplinary Cell growth Interleukin-17 Experimental autoimmune encephalomyelitis Granulocyte-Macrophage Colony-Stimulating Factor FOXP3 Peripheral tolerance Forkhead Transcription Factors hemic and immune systems Receptors Interleukin medicine.disease Peptide Fragments Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Immunology biology.protein Cancer research Th17 Cells Myelin-Oligodendrocyte Glycoprotein Signal Transduction 030215 immunology

description

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.

year	journal	country	edition	language
2016-08-25	Proceedings of the National Academy of Sciences

https://doi.org/10.1073/pnas.1523869113