The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.

The aryl hydrocarbon receptor (AhR) has been shown to be required for optimal Thelper (Th) 17 cell activation. Th17 cells provide immunity against extracellular pathogens and are implicated in autoimmune diseases. Herein, the role of the AhR in cytokine production by Th17, and by the analogous popul...

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Main Authors: Mark D Hayes, Vitalijs Ovcinnikovs, Andrew G Smith, Ian Kimber, Rebecca J Dearman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4159274?pdf=render
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spelling doaj-d1d3a763c68e4fe2926ec15da99b41922020-11-25T02:33:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10695510.1371/journal.pone.0106955The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.Mark D HayesVitalijs OvcinnikovsAndrew G SmithIan KimberRebecca J DearmanThe aryl hydrocarbon receptor (AhR) has been shown to be required for optimal Thelper (Th) 17 cell activation. Th17 cells provide immunity against extracellular pathogens and are implicated in autoimmune diseases. Herein, the role of the AhR in cytokine production by Th17, and by the analogous population of T cytotoxic (Tc)17 cells, has been examined. Lymph node Tc (CD8(+)) and Th (CD4(+)) cells were isolated by negative selection from naive AhR(+/-) and AhR(-/-) mice and polarised to Tc1/Th1 or Tc17/Th17 phenotypes with appropriate cytokines. Cell differentiation was assessed as a function of mRNA and protein (ELISA and flow cytometry) expression for interferon (IFN)-γ and for key Th17 cytokines. In AhR(+/-) mice, Th17 cells displayed an exclusive IL-17 profile, which was markedly inhibited by a selective AhR antagonist to levels observed in AhR knockout mice. Addition of the natural AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ) markedly enhanced Th17 cell activity in the heterozygotes. In contrast, Tc17 cells polarised into 3 distinct subsets: producing either IL-17 or IFN-γ alone, or both cytokines. Blocking AhR was also detrimental to Tc17 development, with reduced responses recorded in AhR(-/-) mice and antagonist-mediated reduction of IL-17 expression in the heterozygotes. However, Tc17 cells were largely refractory to exogenous FICZ, presumably because Tc17 cells express baseline AhR mRNA, but unlike Th17 cells, there is no marked up-regulation during polarisation. Thus, Th17 cell development is more dependent upon AhR activation than is Tc17 cell development, suggesting that endogenous AhR ligands play a much greater role in driving Th17 cell responses.http://europepmc.org/articles/PMC4159274?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Mark D Hayes
Vitalijs Ovcinnikovs
Andrew G Smith
Ian Kimber
Rebecca J Dearman
spellingShingle Mark D Hayes
Vitalijs Ovcinnikovs
Andrew G Smith
Ian Kimber
Rebecca J Dearman
The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.
PLoS ONE
author_facet Mark D Hayes
Vitalijs Ovcinnikovs
Andrew G Smith
Ian Kimber
Rebecca J Dearman
author_sort Mark D Hayes
title The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.
title_short The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.
title_full The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.
title_fullStr The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.
title_full_unstemmed The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.
title_sort aryl hydrocarbon receptor: differential contribution to t helper 17 and t cytotoxic 17 cell development.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2014-01-01
description The aryl hydrocarbon receptor (AhR) has been shown to be required for optimal Thelper (Th) 17 cell activation. Th17 cells provide immunity against extracellular pathogens and are implicated in autoimmune diseases. Herein, the role of the AhR in cytokine production by Th17, and by the analogous population of T cytotoxic (Tc)17 cells, has been examined. Lymph node Tc (CD8(+)) and Th (CD4(+)) cells were isolated by negative selection from naive AhR(+/-) and AhR(-/-) mice and polarised to Tc1/Th1 or Tc17/Th17 phenotypes with appropriate cytokines. Cell differentiation was assessed as a function of mRNA and protein (ELISA and flow cytometry) expression for interferon (IFN)-γ and for key Th17 cytokines. In AhR(+/-) mice, Th17 cells displayed an exclusive IL-17 profile, which was markedly inhibited by a selective AhR antagonist to levels observed in AhR knockout mice. Addition of the natural AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ) markedly enhanced Th17 cell activity in the heterozygotes. In contrast, Tc17 cells polarised into 3 distinct subsets: producing either IL-17 or IFN-γ alone, or both cytokines. Blocking AhR was also detrimental to Tc17 development, with reduced responses recorded in AhR(-/-) mice and antagonist-mediated reduction of IL-17 expression in the heterozygotes. However, Tc17 cells were largely refractory to exogenous FICZ, presumably because Tc17 cells express baseline AhR mRNA, but unlike Th17 cells, there is no marked up-regulation during polarisation. Thus, Th17 cell development is more dependent upon AhR activation than is Tc17 cell development, suggesting that endogenous AhR ligands play a much greater role in driving Th17 cell responses.
url http://europepmc.org/articles/PMC4159274?pdf=render
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