CD5 ENHANCES TH17 DIFFERENTIATION BY REGULATING IFN-γ RESPONSE AND RORγT LOCALIZATION

Mechanisms that modulate the generation of Th17 cells are incompletely understood. We report that the activation of CK2 by CD5 is essential for the efficient generation of Th17 cells in vitro and in vivo . The CD5-CK2 signaling pathway enhanced TCR induced activation of AKT and promoted the differen...

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Published in:European journal of immunology 2014-01, Vol.44 (4), p.1137-1142
Main Authors: McGuire, Donald J., Rowse, Amber L., Li, Hao, Peng, Binghao J., Sestero, Christine M., Cashman, Kevin S., De Sarno, Patrizia, Raman, Chander
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container_issue 4
container_start_page 1137
container_title European journal of immunology
container_volume 44
creator McGuire, Donald J.
Rowse, Amber L.
Li, Hao
Peng, Binghao J.
Sestero, Christine M.
Cashman, Kevin S.
De Sarno, Patrizia
Raman, Chander
description Mechanisms that modulate the generation of Th17 cells are incompletely understood. We report that the activation of CK2 by CD5 is essential for the efficient generation of Th17 cells in vitro and in vivo . The CD5-CK2 signaling pathway enhanced TCR induced activation of AKT and promoted the differentiation of Th17 cells by two independent mechanisms: inhibiting GSK3, and activating mTOR. Genetic ablation of the CD5-CK2 signaling pathway attenuated TCR induced AKT activation and consequently increased activity of GSK3 in Th17 cells. This resulted in Th17 cells being more sensitive to IFN-γ mediated inhibition. In the absence of CD5-CK2 signaling, we observed decreased activity of S6K and attenuated nuclear translocation of RORγt. These results reveal a novel and essential function of CD5-CK2 signaling pathway and GSK3-IFNγ axis in regulating Th differentiation and provide a possible means to dampen Th17 responses in autoimmune diseases.
doi_str_mv 10.1002/eji.201343998
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title CD5 ENHANCES TH17 DIFFERENTIATION BY REGULATING IFN-γ RESPONSE AND RORγT LOCALIZATION
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