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Nature Research, Nature Communications, 1(6), 2015

DOI: 10.1038/ncomms7801

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

Journal article published in 2015 by Lise Lefèvre, Sokrates Stein ORCID, Hélène Authier ORCID, Clarisse Majorel, Bettina Couderc, Christophe Dardenne, Mohamad Ala Eddine, Eddine Ma, Etienne Meunier, José Bernad, Alexis Valentin ORCID, Bernard Pipy ORCID, Kristina Schoonjans, Agnès Coste ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractLiver 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.