| First Author | Wachowicz K | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 5 | Pages | e96401 |
| PubMed ID | 24788550 | Mgi Jnum | J:216101 |
| Mgi Id | MGI:5607699 | Doi | 10.1371/journal.pone.0096401 |
| Citation | Wachowicz K, et al. (2014) Protein kinase C theta regulates the phenotype of murine CD4+ Th17 cells. PLoS One 9(5):e96401 |
| abstractText | Protein kinase C theta (PKCtheta) is involved in signaling downstream of the T cell antigen receptor (TCR) and is important for shaping effector T cell functions and inflammatory disease development. Acquisition of Th1-like effector features by Th17 cells has been linked to increased pathogenic potential. However, the molecular mechanisms underlying Th17/Th1 phenotypic instability remain largely unknown. In the current study, we address the role of PKCtheta in differentiation and function of Th17 cells by using genetic knock-out mice. Implementing in vitro (polarizing T cell cultures) and in vivo (experimental autoimmune encephalomyelitis model, EAE) techniques, we demonstrated that PKCtheta-deficient CD4+ T cells show normal Th17 marker gene expression (interleukin 17A/F, RORgammat), accompanied by enhanced production of the Th1-typical markers such as interferon gamma (IFN-gamma) and transcription factor T-bet. Mechanistically, this phenotype was linked to aberrantly elevated Stat4 mRNA levels in PKCtheta-/- CD4+ T cells during the priming phase of Th17 differentiation. In contrast, transcription of the Stat4 gene was suppressed in Th17-primed wild-type cells. This change in cellular effector phenotype was reflected in vivo by prolonged neurological impairment of PKCtheta-deficient mice during the course of EAE. Taken together, our data provide genetic evidence that PKCtheta is critical for stabilizing Th17 cell phenotype by selective suppression of the STAT4/IFN-gamma/T-bet axis at the onset of differentiation. |
