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

Wanda Niedbala, Anne-Gaelle Besnard, Hui R. Jiang, Jose C. Alves-Filho, Sandra Y. Fukada, Daniela Nascimento, Akio Mitani, Peter Pushparaj, Mohammed H. Alqahtani, Foo Y. Liew

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)164-170
Number of pages7
JournalJournal of Immunology
Volume191
Issue number1
DOIs
Publication statusPublished - 1 Jul 2013

Keywords

  • free radical
  • retinoic acid–related orphan receptor
  • autoimmune encephalomyelitis

Cite this

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