The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear. Flow and imaging cytometry were used to determine the relative expression of CD81 and CXCR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in X -reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses. In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CXCR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts. We identified CD81 and CXCR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.

中文翻译：

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肾脏驻留巨噬细胞具有独特的亚群和多功能作用


肾脏包含不同的肾小球和肾小管间质室，具有不同的细胞类型和细胞外基质成分。免疫细胞在肾小球环境中的作用对于抑制炎症和维持体内平衡至关重要。巨噬细胞是受组织微环境影响的先天免疫细胞。然而，肾脏巨噬细胞的多功能作用仍不清楚。使用流式细胞术和成像细胞术测定肾脏巨噬细胞中 CD81 和 CXCR1（C-X3-C 基序趋化因子受体 1）的相对表达。在X-报告基因小鼠和屏蔽嵌合小鼠中评估单核细胞补充。对野生型和 (Alport) 小鼠分离的肾脏巨噬细胞进行大量 RNA 测序和基于质谱的蛋白质组学分析。 RNAscope 用于可视化通过 CIBERSORTx 分析评估的大量 RNA 中的转录本和巨噬细胞纯度。在野生型小鼠中，我们使用 CD81 和 CXCR1 鉴定了三个不同的肾脏巨噬细胞亚群，这些亚群显示出对单核细胞补充的依赖。除了免疫功能外，巨噬细胞的大量 RNA 测序还显示出与细胞外基质相关的生物过程的富集。蛋白质组学鉴定了野生型小鼠肾脏巨噬细胞中的胶原蛋白 IV 和层粘连蛋白，而 (Alport) 小鼠中则富集了其他细胞外基质蛋白，包括组织蛋白酶、ANXA2 和 LAMP2。肾巨噬细胞的一个子集共表达基质和巨噬细胞转录物。我们鉴定出 CD81 和 CXCR1 阳性肾脏巨噬细胞亚群对单核细胞补充具有明显依赖性。多组学分析表明，这些细胞具有多种功能，强调了巨噬细胞在肾脏健康和疾病中的重要性。