| Nitric Oxide Modulates TGF-{beta}-Directive Signals To Suppress Foxp3+ Regulatory T Cell Differentiation and Potentiate Th1 Development. | |
| | |
MedLine Citation:
|
PMID: 21555530 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
TGF-β can induce Foxp3(+) inducible regulatory T cells (Treg) and also synergize with IL-6 and IL-4 to induce Th17 and Th9 cells. We now report that NO modulates TGF-β activity away from Treg but toward the Th1 lineage. NO potentiated Th1 differentiation in the presence of TGF-β in both IL-12-independent and -dependent fashions by augmenting IFN-γ-activated STAT-1 and T-bet. Differentiation into Treg, Th1, and Th17 lineages could be modulated by NO competing with other cofactors, such as IL-6 and retinoic acid. NO antagonized IL-6 to block TGF-β-directed Th17 differentiation, and together with IL-6, NO suppressed Treg development induced by TGF-β and retinoic acid. Furthermore, we show that physiologically produced NO from TNF and inducible NO synthase-producing dendritic cells can contribute to Th1 development predominating over Treg development through a synergistic activity induced when these cells cocluster with conventional dendritic cells presenting Ag to naive Th cells. This illustrates that NO is another cofactor allowing TGF-β to participate in development of multiple Th lineages and suggests a new mechanism by which NO, which is associated with protection against intracellular pathogens, might maintain effective Th1 immunity. |
| | |
Authors:
|
Seung-Woo Lee; Heonsik Choi; So-Young Eun; Satoshi Fukuyama; Michael Croft |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-5-9 |
Journal Detail:
|
Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
|
Created Date: 2011-5-10 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Lung Neutrophils Facilitate Activation of Naive Antigen-Specific CD4+ T Cells during Mycobacterium t...
Next Document: Tumor Cell Programmed Death Ligand 1-Mediated T Cell Suppression Is Overcome by Coexpression of CD80...