Regulation of type 17 helper T-cell function by nitric oxide during inflammation

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 incr...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-05, Vol.108 (22), p.9220-9225
Main Authors: Niedbala, Wanda, Alves-Filho, Jose C, Fukada, Sandra Y, Vieira, Silvio Manfredo, Mitani, Akio, Sonego, Fabiane, Mirchandani, Ananda, Nascimento, Daniele C, Cunha, Fernando Q, Liew, Foo Y
Format: Article
Language:English
Subjects:
Animals
Aryl hydrocarbon receptors
Autoimmune diseases
Autoimmune Diseases - metabolism
Biological Sciences
CD4-positive T-lymphocytes
Cell Proliferation
Cellular biology
Cellular differentiation
Cultured cells
Cyclic GMP - metabolism
Cytochrome P-450 CYP1A1 - metabolism
Cytochrome P450
Cytokines
Dioxin
dioxins
encephalitis
Environmental factors
Experimental allergic encephalomyelitis
Experimental autoimmune encephalomyelitis
Gene expression
Helper cells
Humans
inducible nitric oxide synthase
Inflammation
Inflammatory diseases
Interleukin 22
Interleukin 23
Interleukin-10 - metabolism
interleukin-17
Interleukin-2 - metabolism
Interleukins - metabolism
Ligands
Lymphocytes T
Messenger RNA
Mice
Mice, Inbred BALB C
Models, Biological
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - metabolism
Nitric-oxide synthase
Oxides
Pathogenesis
Polarization
Pollutants
Proto-Oncogene Protein c-ets-1 - metabolism
Receptors, Interleukin - metabolism
Rodents
T cell receptors
T lymphocytes
T-Lymphocytes, Helper-Inducer - cytology
Th17 Cells - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1100667108