Unknown

Dataset Information

0

T cell–derived inducible nitric oxide synthase switches off Th17 cell differentiation.


ABSTRACT: ROR?t is necessary for the generation of TH17 cells but the molecular mechanisms for the regulation of TH17 cells are still not fully understood. We show that activation of CD4? T cells results in the expression of inducible nitric oxide synthase (iNOS). iNOS-deficient mice displayed enhanced T(H)17 cell differentiation but without major effects on either T(H)1 or T(H)2 cell lineages, whereas endothelial NOS (eNOS) or neuronal NOS (nNOS) mutant mice showed comparable T(H)17 cell differentiation compared with wild-type control mice. The addition of N6-(1-iminoethyl)-l-lysine dihydrochloride (L-NIL), the iNOS inhibitor, significantly enhanced TH17 cell differentiation, and S-nitroso-N-acetylpenicillamine (SNAP), the NO donor, dosedependently reduced the percentage of IL-17–producing CD4? T cells. NO mediates nitration of tyrosine residues in ROR?t, leading to the suppression of ROR?t-induced IL-17 promoter activation, indicating that NO regulates IL-17 expression at the transcriptional level. Finally, studies of an experimental model of colitis showed that iNOS deficiency results in more severe inflammation with an enhanced T(H)17 phenotype. These results suggest that NO derived from iNOS in activated T cells plays a negative role in the regulation of T(H)17 cell differentiation and highlight the importance of intrinsic programs for the control of T(H)17 immune responses.

SUBMITTER: Jianjun Yang 

PROVIDER: S-EPMC3698516 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


RORγt is necessary for the generation of TH17 cells but the molecular mechanisms for the regulation of TH17 cells are still not fully understood. We show that activation of CD4⁺ T cells results in the expression of inducible nitric oxide synthase (iNOS). iNOS-deficient mice displayed enhanced T(H)17 cell differentiation but without major effects on either T(H)1 or T(H)2 cell lineages, whereas endothelial NOS (eNOS) or neuronal NOS (nNOS) mutant mice showed comparable T(H)17 cell differentiation  ...[more]

Similar Datasets

| S-EPMC4389243 | biostudies-literature
2015-02-02 | GSE65436 | GEO
| S-EPMC6920088 | biostudies-literature
2015-02-02 | E-GEOD-65436 | biostudies-arrayexpress
| S-EPMC3424351 | biostudies-literature
| S-EPMC2552398 | biostudies-literature
| S-EPMC4712158 | biostudies-literature
| S-EPMC6908786 | biostudies-literature
| S-EPMC4387900 | biostudies-literature
| S-EPMC5485952 | biostudies-literature