Availability of an inflammatory macrophage niche drives phenotypic and functional alterations in Kupffer cells
Availability of an inflammatory macrophage niche drives phenotypic and functional alterations in Kupffer cells
Abstract Inflammatory signals lead to recruitment of circulating monocytes and induce their differentiation into disease-associated macrophages1–3. Therefore, whether blocking inflammatory monocytes can mitigate disease progression is being actively evaluated4. Here, we employed multiple lineage tracing models and confirmed that monocyte-derived macrophages (mo-macs) are the major population of liver metastasis-associated macrophages (LMAMs), while the population of Kupffer cells (KCs), liver-resident macrophages, is diminished in liver metastatic nodules. Paradoxically, genetic ablation of mo-macs resulted in only a marginal decrease in LMAMs. Using a proliferation recording system and a KC tracing model in a monocyte-deficient background, we found that LMAMs can be replenished either via increased local macrophage proliferation or by promoting KC infiltration. After occupying macrophage niches left vacant by monocyte depletion, KCs exhibit substantial phenotypic and functional alterations through epigenetic reprogramming. These data suggest that dual blockade of monocytes and macrophages could be used to effectively target immunosuppressive myelopoiesis and to reprogram the microenvironment towards an immunostimulatory state.
Chen Yan-Zhou、Tian Lin、Ju Huai-Qiang、Huang Han-Ying、Yue Jia-Xing、Zheng Xin-Nan、Shi Yan-Xia
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer||Department of Hematologic Oncology, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer||Department of Medical Oncology, Sun Yat-sen University Cancer Center
基础医学肿瘤学生物科学研究方法、生物科学研究技术
Chen Yan-Zhou,Tian Lin,Ju Huai-Qiang,Huang Han-Ying,Yue Jia-Xing,Zheng Xin-Nan,Shi Yan-Xia.Availability of an inflammatory macrophage niche drives phenotypic and functional alterations in Kupffer cells[EB/OL].(2025-03-28)[2025-06-30].https://www.biorxiv.org/content/10.1101/2024.04.23.590829.点此复制
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