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