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E-GEOD-23505 - Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-β Signaling

Status
Released on 31 August 2010, last updated on 27 March 2012
Organism
Mus musculus
Samples (10)
Array (1)
Protocols (7)
Description
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
Experiment type
transcription profiling by array 
Contacts
Lai Wei <weil2@mail.nih.gov>, Arian Laurence, Cristina M Tato, Daniel J Cua, Ethan Shevach, Gérard Eberl, Haydeé L Ramos, Hong-Wei Sun, Joanne Konkel, John Grainger, John J O’Shea, Kamran Ghoreschi, Mandy J McGeachy, Nicolas Bouladoux, Qian Chen, Todd Davidson, Wanjun Chen, Wendy T Watford, Xiang-Ping Yang, Yasmine Belkaid, Yuka Kanno
Citation
Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling. Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel JE, Ramos HL, Wei L, Davidson TS, Bouladoux N, Grainger JR, Chen Q, Kanno Y, Watford WT, Sun HW, Eberl G, Shevach EM, Belkaid Y, Cua DJ, Chen W, O'Shea JJ. , PMID:20962846
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-23505.idf.txt
Sample and data relationshipE-GEOD-23505.sdrf.txt
Raw data (1)E-GEOD-23505.raw.1.zip
Processed data (1)E-GEOD-23505.processed.1.zip
Array designA-AFFY-45.adf.txt
R ExpressionSetE-GEOD-23505.eSet.r
Links