biostudies-literatureHuang HYNational Natural Science Foundation of China (National Science Foundation of China)9337https://www.ebi.ac.uk/biostudies/studies/S-EPMC11522483biostudies-literatureUnknown15(1)Inflammatory signals lead to recruitment of circulating monocytes and induce their differentiation into pro-inflammatory macrophages. Therefore, whether blocking inflammatory monocytes can mitigate disease progression is being actively evaluated. Here, we employ multiple lineage-tracing models and show that monocyte-derived macrophages (mo-mac) are the major population of immunosuppressive, liver metastasis-associated macrophages (LMAM), while the proportion of Kupffer cells (KC) as liver-resident macrophages is diminished in metastatic nodules. Paradoxically, genetic ablation of mo-macs results in only a marginal decrease in LMAMs. Using a proliferation-recording system and a KC-tracing model in a monocyte-deficient background, we find that LMAMs can be replenished either via increased loNature communicationsAlternations in inflammatory macrophage niche drive phenotypic and functional plasticity of Kupffer cells.PMC1152248382173278Tian LZhao CHuang HYJu HQShi YXChen YZYue JXYu KZheng XNfalseAlternations in inflammatory macrophage niche drive phenotypic and functional plasticity of Kupffer cells.Inflammatory signals lead to recruitment of circulating monocytes and induce their differentiation into pro-inflammatory macrophages. Therefore, whether blocking inflammatory monocytes can mitigate disease progression is being actively evaluated. Here, we employ multiple lineage-tracing models and show that monocyte-derived macrophages (mo-mac) are the major population of immunosuppressive, liver metastasis-associated macrophages (LMAM), while the proportion of Kupffer cells (KC) as liver-resident macrophages is diminished in metastatic nodules. Paradoxically, genetic ablation of mo-macs results in only a marginal decrease in LMAMs. Using a proliferation-recording system and a KC-tracing model in a monocyte-deficient background, we find that LMAMs can be replenished either via increased lo2024-01-01T00:00:00Z2024 Oct2026-07-16T03:10:11.412Z2025-04-04T01:59:57.4ZS-EPMC115224833947243510.1038/s41467-024-53659-7