Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10145-50. doi: 10.1073/pnas.1523869113. Epub 2016 Aug 23.

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

Author information

1
Institute for Immunology, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany;
2
Department of Neurology, University Medical Center Mainz of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany;
3
Institute of Organic Chemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany;
4
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany.
5
Institute for Immunology, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany; boppt@uni-mainz.de.

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.

KEYWORDS:

FOXP3; MS therapy; TH17 cells; multiple sclerosis; regulatory T cells

Comment in

PMID:
27555590
PMCID:
PMC5018788
DOI:
10.1073/pnas.1523869113
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center