title: p(⁷⁰S⁶K¹) in the TORC1 pathway is essential for the differentiation of Th17 Cells, but not Th1, Th2, or Treg cells in mice.
abstract: The TORC1 pathway is necessary for ribosomal biogenesis and initiation of protein translation. Furthermore, the differentiation of Th1 and Th17 cells requires TORC1 activity. To investigate the role of the TORC1 pathway in the differentiation of Th1 and/or Th17 cells in more detail, we compared the differentiation capacity of naïve T cells from wild type and p70(S6K1) knockout mice. Expression of many of the genes associated with Th17-cell differentiation, such as IL17a, IL17f, and IL-23R, were reduced in p70(S6K1) knockout mice. In contrast, the development of Th1, Th2, and Treg cells was unaffected in the absence of p70(S6K1) . Furthermore, expression of the major transcription factor in Th17-cell differentiation, retinoic acid receptor-related orphan receptor gamma T, remained unchanged. However, the acetylation of histone 3 at the promoters of IL17a and IL17f was reduced in the absence of p70(S6K1) . In accordance with the in vitro data, the kinetics, but not the development, of EAE was affected with the loss of p70(S6K1) expression. Collectively, our findings suggested that both in vitro and in vivo differentiation of Th17 cells were positively regulated by p70(S6K1) .
authors.affiliation: Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Carl Y
authors.initials: CY
authors.lastname: Sasaki
authors.affiliation: Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Munk
authors.affiliation: Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Erez
authors.initials: E
authors.lastname: Eitan
authors.affiliation: Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Martindale
authors.affiliation: Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
authors.affiliation: Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Paritosh
authors.initials: P
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D047369:Chromatin Immunoprecipitation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000276:immunology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000276:immunology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: IL-17; T-cell differentiation; mTOR; p70S6K1