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Publication : RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression.

First Author  Casanova-Acebes M Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  1655
PubMed ID  32246014 Mgi Jnum  J:287595
Mgi Id  MGI:6406037 Doi  10.1038/s41467-020-15371-0
Citation  Casanova-Acebes M, et al. (2020) RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression. Nat Commun 11(1):1655
abstractText  Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. TRMs express a molecular program that is mostly shaped by tissue cues. However, TRM identity and the mechanisms that maintain TRMs in tissues remain poorly understood. We recently found that serous-cavity TRMs (LPMs) are highly enriched in RXR transcripts and RXR-response elements. Here, we show that RXRs control mouse serous-macrophage identity by regulating chromatin accessibility and the transcriptional regulation of canonical macrophage genes. RXR deficiency impairs neonatal expansion of the LPM pool and reduces the survival of adult LPMs through excess lipid accumulation. We also find that peritoneal LPMs infiltrate early ovarian tumours and that RXR deletion diminishes LPM accumulation in tumours and strongly reduces ovarian tumour progression in mice. Our study reveals that RXR signalling controls the maintenance of the serous macrophage pool and that targeting peritoneal LPMs may improve ovarian cancer outcomes.
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