Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function

Niedbala, W., Besnard, A.-G., Jiang, H.-R., Alves-Filho, J.C., Fukada, S.Y., Nascimento, D., Mitani, A., Pushparaj, P., Alqahtani, M.H. and Liew, F.Y. (2013) Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function. Journal of Immunology, 191(1), pp. 164-170. (doi: 10.4049/jimmunol.1202580)

Abstract

NO is a free radical with pleiotropic functions. We have shown earlier that NO induces a population of CD4+CD25+Foxp3− regulatory T cells (NO-Tregs) that suppress the functions of CD4+CD25− effector T cells in vitro and in vivo. We report in this study an unexpected finding that NO-Tregs suppressed Th17 but not Th1 cell differentiation and function. In contrast, natural Tregs (nTregs), which suppressed Th1 cells, failed to suppress Th17 cells. Consistent with this observation, NO-Tregs inhibited the expression of retinoic acid–related orphan receptor γt but not T-bet, whereas nTregs suppressed T-bet but not retinoic acid–related orphan receptor γt expression. The NO-Treg–mediated suppression of Th17 was partially cell contact–dependent and was associated with IL-10. In vivo, adoptively transferred NO-Tregs potently attenuated experimental autoimmune encephalomyelitis. The disease suppression was accompanied by a reduction of Th17, but not Th1 cells in the draining lymph nodes, and a decrease in the production of IL-17, but an increase in IL-10 synthesis. Our results therefore demonstrate the differential suppressive function between NO-Tregs and nTregs and indicate specialization of the regulatory mechanism of the immune system.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liew, Prof Foo and Pushparaj, Dr Peter and Besnard, Dr Anne-Gaelle and Niedbala, Dr Wanda and Alves-Filho, Dr Jose and Fukada, Dr Sandra and Jiang, Dr Hui-Rong
• Authors: Niedbala, W., Besnard, A.-G., Jiang, H.-R., Alves-Filho, J.C., Fukada, S.Y., Nascimento, D., Mitani, A., Pushparaj, P., Alqahtani, M.H., and Liew, F.Y.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Immunology
• Journal Abbr.: J. Immunol.
• ISSN: 0022-1767
• ISSN (Online): 1550-6606