| First Author | McGuire DJ | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 4 | Pages | 1137-42 |
| PubMed ID | 24356888 | Mgi Jnum | J:209281 |
| Mgi Id | MGI:5566919 | Doi | 10.1002/eji.201343998 |
| Citation | McGuire DJ, et al. (2014) CD5 enhances Th17-cell differentiation by regulating IFN-gamma response and RORgammat localization. Eur J Immunol 44(4):1137-42 |
| abstractText | 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-gamma-mediated inhibition. In the absence of CD5-CK2 signaling, we observed decreased activity of S6K and attenuated nuclear translocation of RORgammat (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-gamma axis in regulating Th-cell differentiation and provide a possible means to dampen Th17-type responses in autoimmune diseases. |
