Nitric oxide modulates TGF-beta-directive signals to suppress Foxp3+ regulatory T cell differentiation and potentiate Th1 development.
J Immunol
; 186(12): 6972-80, 2011 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-21555530
ABSTRACT
TGF-ß 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-ß activity away from Treg but toward the Th1 lineage. NO potentiated Th1 differentiation in the presence of TGF-ß 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-ß-directed Th17 differentiation, and together with IL-6, NO suppressed Treg development induced by TGF-ß 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-ß 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Fator de Crescimento Transformador beta
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Linfócitos T Reguladores
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Células Th1
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Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos