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.

驻留在组织中的巨噬细胞（TRM）遍布所有组织，并在稳态，免疫和修复中发挥关键作用。TRMs表达的分子程序主要受组织提示的影响。但是，TRM身份和在组织中维持TRM的机制仍然知之甚少。我们最近发现浆液腔体TRM（LPM）在RXR转录本和RXR反应元件中高度丰富。在这里，我们表明RXRs通过调节染色质可及性和规范性巨噬细胞基因的转录调控来控制小鼠浆膜巨噬细胞的身份。RXR缺乏会损害LPM库的新生儿扩展，并通过过多的脂质积聚降低成年LPM的存活率。我们还发现腹膜LPM浸润早期卵巢肿瘤，并且RXR缺失减少了肿瘤中LPM的积累并大大降低了小鼠卵巢肿瘤的进展。我们的研究表明，RXR信号控制浆液性巨噬细胞池的维持，靶向腹膜LPM可能会改善卵巢癌的预后。