Protein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.

Protein 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. H...

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Autores principales:	Katarzyna Wachowicz, Natascha Hermann-Kleiter, Marlies Meisel, Kerstin Siegmund, Nikolaus Thuille, Gottfried Baier
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0527c39ada1f4a6cb2f597609a992302
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spelling	oai:doaj.org-article:0527c39ada1f4a6cb2f597609a9923022021-11-18T08:21:01ZProtein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.1932-620310.1371/journal.pone.0096401https://doaj.org/article/0527c39ada1f4a6cb2f597609a9923022014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24788550/?tool=EBIhttps://doaj.org/toc/1932-6203Protein 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.Katarzyna WachowiczNatascha Hermann-KleiterMarlies MeiselKerstin SiegmundNikolaus ThuilleGottfried BaierPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e96401 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katarzyna Wachowicz Natascha Hermann-Kleiter Marlies Meisel Kerstin Siegmund Nikolaus Thuille Gottfried Baier Protein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.
description	Protein 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.
format	article
author	Katarzyna Wachowicz Natascha Hermann-Kleiter Marlies Meisel Kerstin Siegmund Nikolaus Thuille Gottfried Baier
author_facet	Katarzyna Wachowicz Natascha Hermann-Kleiter Marlies Meisel Kerstin Siegmund Nikolaus Thuille Gottfried Baier
author_sort	Katarzyna Wachowicz
title	Protein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.
title_short	Protein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.
title_full	Protein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.
title_fullStr	Protein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.
title_full_unstemmed	Protein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.
title_sort	protein kinase c θ regulates the phenotype of murine cd4+ th17 cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/0527c39ada1f4a6cb2f597609a992302
work_keys_str_mv	AT katarzynawachowicz proteinkinasecthregulatesthephenotypeofmurinecd4th17cells AT nataschahermannkleiter proteinkinasecthregulatesthephenotypeofmurinecd4th17cells AT marliesmeisel proteinkinasecthregulatesthephenotypeofmurinecd4th17cells AT kerstinsiegmund proteinkinasecthregulatesthephenotypeofmurinecd4th17cells AT nikolausthuille proteinkinasecthregulatesthephenotypeofmurinecd4th17cells AT gottfriedbaier proteinkinasecthregulatesthephenotypeofmurinecd4th17cells
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Protein kinase C θ regulates the phenotype of murine CD4+ Th17 cells.

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