LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
Copyright policy )LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
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.
Chromatin Immunoprecipitation, Blotting, Western, Enzyme-Linked Immunosorbent Assay, Article, Mice, Phagocytosis, Nuclear receptors, Candida albicans, Hydroxyeicosatetraenoic Acids, Cytochrome P-450 CYP1A1, Animals, Humans, Monocytes and macrophages, Interleukin-13, Interleukins, Macrophages, Candidiasis, Flow Cytometry, Gastroenteritis, [SDV] Life Sciences [q-bio], PPAR gamma, Phenotype, Cytochrome P-450 CYP1B1, Macrophages, Peritoneal, Cytokines
Chromatin Immunoprecipitation, Blotting, Western, Enzyme-Linked Immunosorbent Assay, Article, Mice, Phagocytosis, Nuclear receptors, Candida albicans, Hydroxyeicosatetraenoic Acids, Cytochrome P-450 CYP1A1, Animals, Humans, Monocytes and macrophages, Interleukin-13, Interleukins, Macrophages, Candidiasis, Flow Cytometry, Gastroenteritis, [SDV] Life Sciences [q-bio], PPAR gamma, Phenotype, Cytochrome P-450 CYP1B1, Macrophages, Peritoneal, Cytokines
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).56 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!