LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPAR gamma 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 LRH-1 in macrophages impedes IL-13-induced macrophage polarization due to impaired generation of 15-HETE PPAR gamma 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/PPAR gamma axis.


Published in:
Nature Communications, 6, 6801
Year:
2015
Publisher:
London, Nature Publishing Group
ISSN:
2041-1723
Laboratories:




 Record created 2015-05-29, last modified 2018-09-13

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