T cell–derived inducible nitric oxide synthase switches off TH17 cell differentiation

Abstract

Nitric oxide derived from iNOS in activated T cells negatively regulates Th17 cell differentiation.

Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases

“…More recently, a study reported that the expression of iNOS in macrophages and dendritic cells can modulate inflammatory cytokine expression including, TNF-α, IL-6, IL-12p70, and IL-23. Growing evidence supports this notion and suggests that NO may control T helper cell differentiation [34,78] . Indeed, works conducted in an experimental model of colitis showed that an iNOS deficiency aggravated inflammation repetition and increased the percentage of Th17 cells.…”

“…One study conducted using a DSSinduced colitis model found that nitrite administration exerts both preventive and therapeutic effects in colonic inflammation [33] . More recently, iNOS deficiency enhanced the inflammation aggravation in an animal model of colitis through enhancing a Th17 differentiated subset [34] .…”

“…However, an NO donor molecule suppressed the IL-17 production in T cell-deficient NOS cultures and reduced the percentage of IL-17-producing CD4 + T cells. NO has been found to regulate IL-17 expression at the transcriptional level through the nitration of tyrosine residues in RORγt, inhibiting its binding to the promoter region of the IL-17 gene [34] .…”

Re-thinking the functions of IgA+plasma cells

“…C T cells, [131][132][133][134][135] endogenous iNOS activity was shown to be required for the polarization of Th17 and Treg cells, 134,136 suggesting that the magnitude and localization of iNOS activity and NO production is critical for the priming and polarization of the Ag-specific T cell pool. Moreover, iNOS-deficient animals have been shown to have lower serum and intestinal IgA and serum IgG2b.…”

Atividade imunomoduladora do óxido nítrico na resposta <i>in vitro</i> de células mononucleares de recém-natos e adultos.

“…Além da sua clássica atividade microbicida, recentemente, alguns trabalhos vêm demonstrando que outras células (linfócitos T e B, células dendríticas), além de macrófagos e monócitos, são capazes de produzir NO, e que esta molécula pode ter um papel imunomodulador dependendo da sua origem e da concentração em que ele se encontra (BAUER et al, 1997;JIANJUN YANG et al, 2013;NIEDBALA et al, 2007;NIEDBALA et al, 2013;NIEDBALA et al, 2014;WINK et al, 2011). Também já foi mostrado, em modelos animais e em humanos, que linfócitos T CD4+ ativados produzem NO, e este vai mediar a nitração de resíduos tirosínicos do fator de transcrição RORγt (característico de linfócitos Th17), inativando-o.…”