Vol 9: Protein Kinase C Regulates the Phenotype of Murine CD4 Th17 Cells.Report as inadecuate



 Vol 9: Protein Kinase C Regulates the Phenotype of Murine CD4  Th17 Cells.


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This article is from PLoS ONE, volume 9.AbstractProtein kinase C θ PKCθ 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 PKCθ 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 PKCθ-deficient CD4+ T cells show normal Th17 marker gene expression interleukin 17A-F, RORγt, accompanied by enhanced production of the Th1-typical markers such as interferon gamma IFN-γ and transcription factor T-bet. Mechanistically, this phenotype was linked to aberrantly elevated Stat4 mRNA levels in PKCθ−-− 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 PKCθ-deficient mice during the course of EAE. Taken together, our data provide genetic evidence that PKCθ is critical for stabilizing Th17 cell phenotype by selective suppression of the STAT4-IFN-γ-T-bet axis at the onset of differentiation.



Author: Wachowicz, Katarzyna; Hermann-Kleiter, Natascha; Meisel, Marlies; Siegmund, Kerstin; Thuille, Nikolaus; Baier, Gottfried

Source: https://archive.org/







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