Document Detail


Molecular antagonism and plasticity of regulatory and inflammatory T cell programs.
MedLine Citation:
PMID:  18585065     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Regulatory T (Treg) and T helper 17 (Th17) cells were recently proposed to be reciprocally regulated during differentiation. To understand the underlying mechanisms, we utilized a Th17 reporter mouse with a red fluorescent protein (RFP) sequence inserted into the interleukin-17F (IL-17F) gene. Using IL-17F-RFP together with a Foxp3 reporter, we found that the development of Th17 and Foxp3(+) Treg cells was associated in immune responses. Although TGF-beta receptor I signaling was required for both Foxp3 and IL-17 induction, SMAD4 was only involved in Foxp3 upregulation. Foxp3 inhibited Th17 differentiation by antagonizing the function of the transcription factors RORgammat and ROR*. In contrast, IL-6 overcame this suppressive effect of Foxp3 and, together with IL-1, induced genetic reprogramming in Foxp3(+) Treg cells. STAT3 regulated Foxp3 downregulation, whereas STAT3, RORgamma, and ROR* were required for IL-17 expression in Treg cells. Our data demonstrate molecular antagonism and plasticity of Treg and Th17 cell programs.
Authors:
Xuexian O Yang; Roza Nurieva; Gustavo J Martinez; Hong Soon Kang; Yeonseok Chung; Bhanu P Pappu; Bhavin Shah; Seon Hee Chang; Kimberly S Schluns; Stephanie S Watowich; Xin-Hua Feng; Anton M Jetten; Chen Dong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2008-06-26
Journal Detail:
Title:  Immunity     Volume:  29     ISSN:  1097-4180     ISO Abbreviation:  Immunity     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-17     Completed Date:  2008-08-12     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44-56     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / immunology*
Encephalomyelitis, Autoimmune, Experimental / immunology
Female
Flow Cytometry
Immunoprecipitation
Inflammation / immunology*
Interleukin-17 / immunology,  metabolism
Lymphocyte Activation / immunology
Mice
Mice, Transgenic
Polymerase Chain Reaction
Signal Transduction / immunology
T-Lymphocyte Subsets / cytology*,  immunology
T-Lymphocytes, Helper-Inducer / cytology*,  immunology
T-Lymphocytes, Regulatory / cytology*,  immunology
Transduction, Genetic
Transforming Growth Factor beta1 / immunology,  metabolism
Grant Support
ID/Acronym/Agency:
AR050772/AR/NIAMS NIH HHS; CA108454/CA/NCI NIH HHS; R01 AI050746/AI/NIAID NIH HHS; R01 AI050746-01/AI/NIAID NIH HHS; Z01 ES101586-05/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-17; 0/Transforming Growth Factor beta1
Comments/Corrections
Comment In:
Immunotherapy. 2009 Jan;1(1):27-9   [PMID:  20635970 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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