| STAT6-dependent regulation of Th9 development. | |
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MedLine Citation:
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PMID: 22180613 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Th cell effector subsets develop in response to specific cytokine environments. The development of a particular cytokine-secreting pattern requires an integration of signals that may promote the development of opposing pathways. A recent example of this paradigm is the IL-9-secreting Th9 cell that develops in response to TGF-β and IL-4, cytokines that, in isolation, promote the development of inducible regulatory T cells and Th2 cells, respectively. To determine how the balance of these factors results in priming for IL-9 secretion, we examined the effects of each pathway on transcription factors that regulate Th cell differentiation. We demonstrated that TGF-β induces the PU.1-encoding Sfpi1 locus and that this is independent of IL-4-induced STAT6 activation. IL-4-activated STAT6 is required for repressing the expression of T-bet and Foxp3 in Th9 cells, transcription factors that inhibit IL-9 production, and STAT6 is required for the induction of IRF4, which promotes Th9 development. These data established a transcription factor network that regulates IL-9 and demonstrated how combinations of cytokine signals generate cytokine-secreting potential by altering the expression of a panel of transcription factors. |
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Authors:
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Ritobrata Goswami; Rukhsana Jabeen; Ryoji Yagi; Duy Pham; Jinfang Zhu; Shreevrat Goenka; Mark H Kaplan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2011-12-16 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 188 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-20 Completed Date: 2012-06-11 Revised Date: 2013-04-08 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 968-75 Citation Subset: AIM; IM |
Affiliation:
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Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation Cytokines Gene Regulatory Networks Interferon Regulatory Factors / genetics Interleukin-4 / immunology Interleukin-9 / secretion* Mice Proto-Oncogene Proteins / genetics STAT6 Transcription Factor / physiology* Signal Transduction / immunology T-Lymphocytes, Helper-Inducer / cytology, secretion* Trans-Activators / genetics Transcriptional Activation |
| Grant Support | |
ID/Acronym/Agency:
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AI057459/AI/NIAID NIH HHS; HL093105/HL/NHLBI NIH HHS; R01 AI057459-06/AI/NIAID NIH HHS; R01 AI057459-07/AI/NIAID NIH HHS; ZIA AI001169-01/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Interferon Regulatory Factors; 0/Interleukin-9; 0/Proto-Oncogene Proteins; 0/STAT6 Transcription Factor; 0/Stat6 protein, mouse; 0/Trans-Activators; 0/interferon regulatory factor-4; 0/proto-oncogene protein Spi-1; 207137-56-2/Interleukin-4 |
| Comments/Corrections | |
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