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.
Highlights
Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair
Circulating monocytes (Supplementary Fig. 1d) and other TRMs (Supplementary Fig. 1b) remained unaffected. In light of these results, we focused our study on serous macrophages
TRMs are known to persist in tissues for prolonged periods, the mechanisms that promote the homeostasis and maintenance of these cells remain unclear
Summary
Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. We show that RXRs control mouse serous-macrophage identity by regulating chromatin accessibility and the transcriptional regulation of canonical macrophage genes. Our study reveals that RXR signalling controls the maintenance of the serous macrophage pool and that targeting peritoneal LPMs may improve ovarian cancer outcomes. Tissueresident macrophages (TRMs) arise mainly from embryonic precursors[2] and reside in tissues for prolonged periods, whereas blood-derived macrophages are found mostly in injured tissues[3]. The peritoneal and pleural cavities are small fluid-filled spaces that contain a large population of immune cells, including T and B cells, mastocytes, dendritic cells, monocytes and macrophages[8]. SPMs differentiate from circulating monocytes, in a process reliant on IRF420
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