CD5 Enhances Th17-cell Differentiation by Regulating IFN-γ Response and RORγt Localization

Overview

Journal Eur J Immunol

Specialty Allergy & Immunology

Date 2013 Dec 21

PMID 24356888

Citations 13

Authors

Donald J McGuire

Amber L Rowse

Hao Li

Binghao J Peng

Christine M Sestero

Kevin S Cashman

Patrizia De Sarno

Chander Raman

Affiliations

Soon will be listed here.

Abstract

Mechanisms that modulate the generation of Th17 cells are incompletely understood. We report that the activation of casein kinase 2 (CK2) by CD5 is essential for the efficient generation of Th17 cells in vitro and in vivo. In our study, the CD5-CK2 signaling pathway enhanced TCR-induced activation of AKT and promoted the differentiation of Th17 cells by two independent mechanisms: inhibition of glycogen synthase kinase 3 (GSK3) and activation of 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 increased sensitivity of Th17 cells to IFN-γ-mediated inhibition. In the absence of CD5-CK2 signaling, we observed decreased activity of S6K and attenuated nuclear translocation of RORγt (ROR is retinoic acid receptor related orphan receptor). These results reveal a novel and essential function of the CD5-CK2 signaling pathway and GSK3-IFN-γ axis in regulating Th-cell differentiation and provide a possible means to dampen Th17-type responses in autoimmune diseases.

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