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

María Casanova-Acebes, María Piedad Menéndez-Gutiérrez, Jesús Porcuna, Damiana Álvarez-Errico, Yonit Lavin, Ana García, Soma Kobayashi, Jessica Le Berichel, Vanessa Núñez, Felipe Were, Daniel Jiménez-Carretero, Fátima Sánchez-Cabo, Miriam Merad () and Mercedes Ricote ()
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María Casanova-Acebes: Icahn School of Medicine at Mount Sinai
María Piedad Menéndez-Gutiérrez: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Jesús Porcuna: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Damiana Álvarez-Errico: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Yonit Lavin: Icahn School of Medicine at Mount Sinai
Ana García: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Soma Kobayashi: Icahn School of Medicine at Mount Sinai
Jessica Le Berichel: Icahn School of Medicine at Mount Sinai
Vanessa Núñez: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Felipe Were: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Daniel Jiménez-Carretero: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Fátima Sánchez-Cabo: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Miriam Merad: Icahn School of Medicine at Mount Sinai
Mercedes Ricote: Centro Nacional de Investigaciones Cardiovasculares (CNIC)

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15371-0

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