Transcriptomics

Dataset Information

68

Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-β Signaling


ABSTRACT: CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies. Mouse T helper 17 cell differentiation with or without TGFB

ORGANISM(S): Mus musculus  

SUBMITTER: Hong-Wei Sun   Arian Laurence  Kamran Ghoreschi  John Grainger  Xiang-Ping Yang  Wanjun Chen  Nicolas Bouladoux  Joanne Konkel  Yasmine Belkaid  Mandy J McGeachy  Daniel J Cua  Todd Davidson  Wendy T Watford  Cristina M Tato  John J O’Shea  Haydeé L Ramos  Lai Wei  Yuka Kanno  Ethan Shevach  Gérard Eberl  Qian Chen 

PROVIDER: E-GEOD-23505 | ArrayExpress | 2010-08-31

SECONDARY ACCESSION(S): GSE23505PRJNA131077

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications


CD4(+) T-helper cells that selectively produce interleukin (IL)-17 (T(H)17), are critical for host defence and autoimmunity. Although crucial for T(H)17 cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been proposed to be the factors responsible for initiating specification. Here we show that T(H)17 differentiation can occur in the absence of TGF-β signalling. Neither IL-6 nor IL-23 alone efficient  ...[more]

Similar Datasets

2010-08-31 | E-GEOD-23681 | ArrayExpress
2010-08-31 | GSE23681 | GEO
2010-08-31 | GSE23505 | GEO
2012-09-01 | E-GEOD-39820 | ArrayExpress
2016-06-15 | E-GEOD-75724 | ArrayExpress
2011-02-09 | E-GEOD-26551 | ArrayExpress
2014-04-17 | E-GEOD-56018 | ArrayExpress
2014-04-17 | E-GEOD-56019 | ArrayExpress
2011-02-09 | E-GEOD-26552 | ArrayExpress
2014-04-17 | E-GEOD-56240 | ArrayExpress