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LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis

Liver receptor homologue-1 (LRH-1) is a nuclear receptor involved in the repression of inflammatory processes in the hepatointestinal tract. Here we report that LRH-1 is expressed in macrophages and induced by the Th2 cytokine IL-13 via a mechanism involving STAT6. We show that loss-of-function of L...

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Autores principales: Lefèvre, Lise, Authier, Hélène, Stein, Sokrates, Majorel, Clarisse, Couderc, Bettina, Dardenne, Christophe, Eddine, Mohamad Ala, Meunier, Etienne, Bernad, José, Valentin, Alexis, Pipy, Bernard, Schoonjans, Kristina, Coste, Agnès
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410638/
https://www.ncbi.nlm.nih.gov/pubmed/25873311
http://dx.doi.org/10.1038/ncomms7801
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author Lefèvre, Lise
Authier, Hélène
Stein, Sokrates
Majorel, Clarisse
Couderc, Bettina
Dardenne, Christophe
Eddine, Mohamad Ala
Meunier, Etienne
Bernad, José
Valentin, Alexis
Pipy, Bernard
Schoonjans, Kristina
Coste, Agnès
author_facet Lefèvre, Lise
Authier, Hélène
Stein, Sokrates
Majorel, Clarisse
Couderc, Bettina
Dardenne, Christophe
Eddine, Mohamad Ala
Meunier, Etienne
Bernad, José
Valentin, Alexis
Pipy, Bernard
Schoonjans, Kristina
Coste, Agnès
author_sort Lefèvre, Lise
collection PubMed
description Liver receptor homologue-1 (LRH-1) is a nuclear receptor involved in the repression of inflammatory processes in the hepatointestinal tract. Here we report that LRH-1 is expressed in macrophages and induced by the Th2 cytokine IL-13 via a mechanism involving STAT6. We show that loss-of-function of LRH-1 in macrophages impedes IL-13-induced macrophage polarization due to impaired generation of 15-HETE PPARγ ligands. The incapacity to generate 15-HETE metabolites is at least partially caused by the compromised regulation of CYP1A1 and CYP1B1. Mice with LRH-1-deficient macrophages are, furthermore, highly susceptible to gastrointestinal and systemic Candida albicans infection. Altogether, these results identify LRH-1 as a critical component of the anti-inflammatory and fungicidal response of alternatively activated macrophages that acts upstream from the IL-13-induced 15-HETE/PPARγ axis.
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spelling pubmed-44106382015-05-08 LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis Lefèvre, Lise Authier, Hélène Stein, Sokrates Majorel, Clarisse Couderc, Bettina Dardenne, Christophe Eddine, Mohamad Ala Meunier, Etienne Bernad, José Valentin, Alexis Pipy, Bernard Schoonjans, Kristina Coste, Agnès Nat Commun Article Liver receptor homologue-1 (LRH-1) is a nuclear receptor involved in the repression of inflammatory processes in the hepatointestinal tract. Here we report that LRH-1 is expressed in macrophages and induced by the Th2 cytokine IL-13 via a mechanism involving STAT6. We show that loss-of-function of LRH-1 in macrophages impedes IL-13-induced macrophage polarization due to impaired generation of 15-HETE PPARγ ligands. The incapacity to generate 15-HETE metabolites is at least partially caused by the compromised regulation of CYP1A1 and CYP1B1. Mice with LRH-1-deficient macrophages are, furthermore, highly susceptible to gastrointestinal and systemic Candida albicans infection. Altogether, these results identify LRH-1 as a critical component of the anti-inflammatory and fungicidal response of alternatively activated macrophages that acts upstream from the IL-13-induced 15-HETE/PPARγ axis. Nature Pub. Group 2015-04-15 /pmc/articles/PMC4410638/ /pubmed/25873311 http://dx.doi.org/10.1038/ncomms7801 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lefèvre, Lise
Authier, Hélène
Stein, Sokrates
Majorel, Clarisse
Couderc, Bettina
Dardenne, Christophe
Eddine, Mohamad Ala
Meunier, Etienne
Bernad, José
Valentin, Alexis
Pipy, Bernard
Schoonjans, Kristina
Coste, Agnès
LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
title LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
title_full LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
title_fullStr LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
title_full_unstemmed LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
title_short LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
title_sort lrh-1 mediates anti-inflammatory and antifungal phenotype of il-13-activated macrophages through the pparγ ligand synthesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410638/
https://www.ncbi.nlm.nih.gov/pubmed/25873311
http://dx.doi.org/10.1038/ncomms7801
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