Cargando…

Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation

Retinoic acid (RA), a vitamin A metabolite, modulates mucosal T helper cell responses. Here we examined the role of RA in regulating IL-22 production by γδ T cells and innate lymphoid cells in intestinal inflammation. RA significantly enhanced IL-22 production by γδ T cells stimulated in vitro with...

Descripción completa

Detalles Bibliográficos
Autores principales: Mielke, Lisa A., Jones, Sarah A., Raverdeau, Mathilde, Higgs, Rowan, Stefanska, Anna, Groom, Joanna R., Misiak, Alicja, Dungan, Lara S., Sutton, Caroline E., Streubel, Gundula, Bracken, Adrian P., Mills, Kingston H.G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674702/
https://www.ncbi.nlm.nih.gov/pubmed/23690441
http://dx.doi.org/10.1084/jem.20121588
_version_ 1782272408270405632
author Mielke, Lisa A.
Jones, Sarah A.
Raverdeau, Mathilde
Higgs, Rowan
Stefanska, Anna
Groom, Joanna R.
Misiak, Alicja
Dungan, Lara S.
Sutton, Caroline E.
Streubel, Gundula
Bracken, Adrian P.
Mills, Kingston H.G.
author_facet Mielke, Lisa A.
Jones, Sarah A.
Raverdeau, Mathilde
Higgs, Rowan
Stefanska, Anna
Groom, Joanna R.
Misiak, Alicja
Dungan, Lara S.
Sutton, Caroline E.
Streubel, Gundula
Bracken, Adrian P.
Mills, Kingston H.G.
author_sort Mielke, Lisa A.
collection PubMed
description Retinoic acid (RA), a vitamin A metabolite, modulates mucosal T helper cell responses. Here we examined the role of RA in regulating IL-22 production by γδ T cells and innate lymphoid cells in intestinal inflammation. RA significantly enhanced IL-22 production by γδ T cells stimulated in vitro with IL-1β or IL-18 and IL-23. In vivo RA attenuated colon inflammation induced by dextran sodium sulfate treatment or Citrobacter rodentium infection. This was associated with a significant increase in IL-22 secretion by γδ T cells and innate lymphoid cells. In addition, RA treatment enhanced production of the IL-22–responsive antimicrobial peptides Reg3β and Reg3γ in the colon. The attenuating effects of RA on colitis were reversed by treatment with an anti–IL-22 neutralizing antibody, demonstrating that RA mediates protection by enhancing IL-22 production. To define the molecular events involved, we used chromatin immunoprecipitation assays and found that RA promoted binding of RA receptor to the IL-22 promoter in γδ T cells. Our findings provide novel insights into the molecular events controlling IL-22 transcription and suggest that one key outcome of RA signaling may be to shape early intestinal immune responses by promoting IL-22 synthesis by γδ T cells and innate lymphoid cells.
format Online
Article
Text
id pubmed-3674702
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-36747022013-12-03 Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation Mielke, Lisa A. Jones, Sarah A. Raverdeau, Mathilde Higgs, Rowan Stefanska, Anna Groom, Joanna R. Misiak, Alicja Dungan, Lara S. Sutton, Caroline E. Streubel, Gundula Bracken, Adrian P. Mills, Kingston H.G. J Exp Med Brief Definitive Report Retinoic acid (RA), a vitamin A metabolite, modulates mucosal T helper cell responses. Here we examined the role of RA in regulating IL-22 production by γδ T cells and innate lymphoid cells in intestinal inflammation. RA significantly enhanced IL-22 production by γδ T cells stimulated in vitro with IL-1β or IL-18 and IL-23. In vivo RA attenuated colon inflammation induced by dextran sodium sulfate treatment or Citrobacter rodentium infection. This was associated with a significant increase in IL-22 secretion by γδ T cells and innate lymphoid cells. In addition, RA treatment enhanced production of the IL-22–responsive antimicrobial peptides Reg3β and Reg3γ in the colon. The attenuating effects of RA on colitis were reversed by treatment with an anti–IL-22 neutralizing antibody, demonstrating that RA mediates protection by enhancing IL-22 production. To define the molecular events involved, we used chromatin immunoprecipitation assays and found that RA promoted binding of RA receptor to the IL-22 promoter in γδ T cells. Our findings provide novel insights into the molecular events controlling IL-22 transcription and suggest that one key outcome of RA signaling may be to shape early intestinal immune responses by promoting IL-22 synthesis by γδ T cells and innate lymphoid cells. The Rockefeller University Press 2013-06-03 /pmc/articles/PMC3674702/ /pubmed/23690441 http://dx.doi.org/10.1084/jem.20121588 Text en © 2013 Mielke et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Mielke, Lisa A.
Jones, Sarah A.
Raverdeau, Mathilde
Higgs, Rowan
Stefanska, Anna
Groom, Joanna R.
Misiak, Alicja
Dungan, Lara S.
Sutton, Caroline E.
Streubel, Gundula
Bracken, Adrian P.
Mills, Kingston H.G.
Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation
title Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation
title_full Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation
title_fullStr Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation
title_full_unstemmed Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation
title_short Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation
title_sort retinoic acid expression associates with enhanced il-22 production by γδ t cells and innate lymphoid cells and attenuation of intestinal inflammation
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674702/
https://www.ncbi.nlm.nih.gov/pubmed/23690441
http://dx.doi.org/10.1084/jem.20121588
work_keys_str_mv AT mielkelisaa retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT jonessaraha retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT raverdeaumathilde retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT higgsrowan retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT stefanskaanna retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT groomjoannar retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT misiakalicja retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT dunganlaras retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT suttoncarolinee retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT streubelgundula retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT brackenadrianp retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation
AT millskingstonhg retinoicacidexpressionassociateswithenhancedil22productionbygdtcellsandinnatelymphoidcellsandattenuationofintestinalinflammation