Open AccessRegulation of type 17 helper T-cell function by nitric oxide during inflammation
Author(s) -
Wanda Niedbała,
José Carlos AlvesFilho,
Sandra Yasuyo Fukada,
Sílvio M. Vieira,
Akio Mitani,
Fabiane Sônego,
Ananda S. Mirchandani,
Daniele C. Nascimento,
Fernando Cunha,
Foo Y. Liew
Publication year - 2011
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1100667108
Subject(s) - aryl hydrocarbon receptor , experimental autoimmune encephalomyelitis , nitric oxide , inflammation , immunology , nitric oxide synthase , autoimmune disease , interleukin 17 , receptor , autoimmunity , pathogenesis , chemistry , t cell , biology , microbiology and biotechnology , immune system , endocrinology , biochemistry , transcription factor , antibody , gene
Type 17 helper T (Th17) cells are implicated in the pathogenesis many of human autoimmune diseases. Development of Th17 can be enhanced by the activation of aryl hydrocarbon receptor (AHR) whose ligands include the environmental pollutant dioxin, potentially linking environmental factors to the increased prevalence of autoimmune disease. We report here that nitric oxide (NO) can suppress the proliferation and function of polarized murine and human Th17 cells. NO also inhibits AHR expression in Th17 cells and the downstream events of AHR activation, including IL-22, IL-23 receptor, and Cyp1a1. Conversely, NO did not affect the polarization of Th17 cells from mice deficient in AHR. Furthermore, mice lacking inducible nitric oxide synthase (Nos2(-/-)) developed more severe experimental autoimmune encephalomyelitis than WT mice, with elevated AHR expression, increased IL-17A, and IL-22 synthesis. NO may therefore represent an important endogenous regulator to prevent overexpansion of Th17 cells and control of autoimmune diseases caused by environmental pollutants.