Niedbala, W., Cai, B., Liu, H., Pitman, N., Chang, L. and Liew, F. Y. (2007) Nitric oxide induces CD4+CD25+ Foxp3− regulatory T cells from CD4+CD25− T cells via p53, IL-2, and OX40. Proceedings of the National Academy of Sciences of the United States of America, 104(39), pp. 15478-15483. (doi: 10.1073/pnas.0703725104)
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Publisher's URL: http://dx.doi.org/10.1073/pnas.0703725104
Abstract
The principal aim of the immune system is to establish a balance between defense against pathogens and avoidance of autoimmune disease. This balance is achieved partly through regulatory T cells (Tregs). CD4<sup>+</sup>CD25<sup>+</sup> Tregs are either naturally occurring or induced by antigens and are characterized by the expression of the X-linked forkhead/winged helix transcription factor, Foxp3. Here we report a previously unrecognized subset of CD4<sup>+</sup> CD25<sup>+</sup> Tregs derived from CD4<sup>+</sup> CD25<sup>−</sup> T cells induced by nitric oxide (NO). The induction of Tregs (NO-Tregs) is independent of cGMP but depends on p53, IL-2, and OX40. NO-Tregs produced IL-4 and IL-10, but not IL-2, IFNγ, or TGFβ. The cells were GITR<sup>+</sup>, CD27<sup>+</sup>, T-bet<sup>low</sup>, GATA3<sup>high</sup>, and Foxp3<sup>−</sup>. NO-Tregs suppressed the proliferation of CD4+CD25− T cells in vitro and attenuated colitis- and collagen-induced arthritis in vivo in an IL-10-dependent manner. NO-Tregs also were induced in vivo in SCID mice adoptively transferred with CD4<sup>+</sup>CD25<sup>−</sup> T cells in the presence of LPS and IFNγ, and the induction was completely inhibited by N <sup>G</sup>-monomethyl-L-arginine, a pan NO synthase inhibitor. Therefore, our findings uncovered a previously unrecognized function of NO via the NO–p53–IL-2–OX40–survivin signaling pathway for T cell differentiation and development.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Liew, Prof Foo and Niedbala, Dr Wanda and Pitman, Dr Nick and Cai, Ms Beilei |
Authors: | Niedbala, W., Cai, B., Liu, H., Pitman, N., Chang, L., and Liew, F. Y. |
College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
Publisher: | National Academy of Sciences |
ISSN: | 0027-8424 |
ISSN (Online): | 1091-6490 |
Published Online: | 17 September 2007 |
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