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

26 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.
LanguageEnglish
Pages164-170
Number of pages7
JournalJournal of Immunology
Volume191
Issue number1
DOIs
Publication statusPublished - 1 Jul 2013

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Th1 Cells
Regulatory T-Lymphocytes
Cell Differentiation
Nitric Oxide
Tretinoin
Interleukin-10
Th17 Cells
Autoimmune Experimental Encephalomyelitis
Interleukin-17
Free Radicals
Immune System
Lymph Nodes
T-Lymphocytes
Population

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., ... 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
Niedbala, Wanda ; Besnard, Anne-Gaelle ; Jiang, Hui R. ; Alves-Filho, Jose C. ; Fukada, Sandra Y. ; Nascimento, Daniela ; Mitani, Akio ; Pushparaj, Peter ; Alqahtani, Mohammed H. ; Liew, Foo Y. / Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function. In: Journal of Immunology . 2013 ; Vol. 191, No. 1. pp. 164-170.
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Niedbala, W, Besnard, A-G, Jiang, HR, Alves-Filho, JC, Fukada, SY, Nascimento, D, Mitani, A, Pushparaj, P, Alqahtani, MH & Liew, FY 2013, 'Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function' Journal of Immunology , vol. 191, no. 1, pp. 164-170. https://doi.org/10.4049/jimmunol.1202580

Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function. / Niedbala, Wanda; Besnard, Anne-Gaelle; Jiang, Hui R.; Alves-Filho, Jose C.; Fukada, Sandra Y.; Nascimento, Daniela; Mitani, Akio; Pushparaj, Peter; Alqahtani, Mohammed H.; Liew, Foo Y.

In: Journal of Immunology , Vol. 191, No. 1, 01.07.2013, p. 164-170.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function

AU - Niedbala, Wanda

AU - Besnard, Anne-Gaelle

AU - Jiang, Hui R.

AU - Alves-Filho, Jose C.

AU - Fukada, Sandra Y.

AU - Nascimento, Daniela

AU - Mitani, Akio

AU - Pushparaj, Peter

AU - Alqahtani, Mohammed H.

AU - Liew, Foo Y.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

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KW - retinoic acid–related orphan receptor

KW - autoimmune encephalomyelitis

U2 - 10.4049/jimmunol.1202580

DO - 10.4049/jimmunol.1202580

M3 - Article

VL - 191

SP - 164

EP - 170

JO - Journal of Immunology

T2 - Journal of Immunology

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