Nitric Oxide Modulates TGF-beta-Directive Signals To Suppress Foxp3(+) Regulatory T Cell Differentiation and Potentiate Th1 Development
SCIE
SCOPUS
- Title
- Nitric Oxide Modulates TGF-beta-Directive Signals To Suppress Foxp3(+) Regulatory T Cell Differentiation and Potentiate Th1 Development
- Authors
- Lee, SW; Choi, H; Eun, SY; Fukuyama, S; Croft, M
- Date Issued
- 2011-06-15
- Publisher
- The American Association of immunologists
- Abstract
- TGF-beta 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-beta activity away from Treg but toward the Th1 lineage. NO potentiated Th1 differentiation in the presence of TGF-beta in both IL-12-independent and -dependent fashions by augmenting IFN-gamma-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-beta-directed Th17 differentiation, and together with IL-6, NO suppressed Treg development induced by TGF-beta 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-beta 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. The Journal of Immunology, 2011, 186: 6972-6980.
- Keywords
- GROWTH-FACTOR-BETA; DENDRITIC CELLS; RETINOIC-ACID; IMMUNE-RESPONSES; IFN-GAMMA; INDUCTION; ACTIVATION; SYNTHASE; T(H)17; IL-2
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/14220
- DOI
- 10.4049/JIMMUNOL.1100485
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- JOURNAL OF IMMUNOLOGY, vol. 186, no. 12, page. 6972 - 6980, 2011-06-15
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