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.
journal_name
Proc Natl Acad Sci U S Aauthors
Ulges A,Witsch EJ,Pramanik G,Klein M,Birkner K,Bühler U,Wasser B,Luessi F,Stergiou N,Dietzen S,Brühl TJ,Bohn T,Bündgen G,Kunz H,Waisman A,Schild H,Schmitt E,Zipp F,Bopp Tdoi
10.1073/pnas.1523869113subject
Has Abstractpub_date
2016-09-06 00:00:00pages
10145-50issue
36eissn
0027-8424issn
1091-6490pii
1523869113journal_volume
113pub_type
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