| First Author | Lefèvre L | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6801 | PubMed ID | 25873311 |
| Mgi Jnum | J:222716 | Mgi Id | MGI:5645421 |
| Doi | 10.1038/ncomms7801 | Citation | Lefevre L, et al. (2015) LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARgamma ligand synthesis. Nat Commun 6:6801 |
| abstractText | 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 PPARgamma 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/PPARgamma axis. |
