Department of Cell, Developmental, and Integrative Biology,
Department of Cell, Developmental, and Integrative Biology.
J Am Soc Nephrol. 2019 May;30(5):767-781. doi: 10.1681/ASN.2018090931. Epub 2019 Apr 4.
Resident macrophages regulate homeostatic and disease processes in multiple tissues, including the kidney. Despite having well defined markers to identify these cells in mice, technical limitations have prevented identification of a similar cell type across species. The inability to identify resident macrophage populations across species hinders the translation of data obtained from animal model to human patients.
As an entry point to determine novel markers that could identify resident macrophages across species, we performed single-cell RNA sequencing (scRNAseq) analysis of all T and B cell-negative CD45 innate immune cells in mouse, rat, pig, and human kidney tissue.
We identified genes with enriched expression in mouse renal resident macrophages that were also present in candidate resident macrophage populations across species. Using the scRNAseq data, we defined a novel set of possible cell surface markers (Cd74 and Cd81) for these candidate kidney resident macrophages. We confirmed, using parabiosis and flow cytometry, that these proteins are indeed enriched in mouse resident macrophages. Flow cytometry data also indicated the existence of a defined population of innate immune cells in rat and human kidney tissue that coexpress CD74 and CD81, suggesting the presence of renal resident macrophages in multiple species.
Based on transcriptional signatures, our data indicate that there is a conserved population of innate immune cells across multiple species that have been defined as resident macrophages in the mouse. Further, we identified potential cell surface markers to allow for future identification and characterization of this candidate resident macrophage population in mouse, rat, and pig translational studies.
驻留巨噬细胞调节包括肾脏在内的多种组织中的稳态和疾病过程。尽管在小鼠中有明确的标记物来识别这些细胞，但技术限制使得在不同物种中无法识别类似的细胞类型。无法在不同物种中识别驻留巨噬细胞群体阻碍了将从动物模型获得的数据转化为人类患者的应用。
作为确定可跨物种识别驻留巨噬细胞的新标记物的切入点，我们对小鼠、大鼠、猪和人肾脏组织中的所有 T 和 B 细胞阴性 CD45 固有免疫细胞进行了单细胞 RNA 测序 (scRNAseq) 分析。
我们鉴定了在小鼠肾脏驻留巨噬细胞中表达丰富的基因，这些基因也存在于候选驻留巨噬细胞群体中。利用 scRNAseq 数据，我们定义了一组新的可能的细胞表面标记物（Cd74 和 Cd81）用于这些候选肾脏驻留巨噬细胞。我们通过并系和流式细胞术证实，这些蛋白确实在小鼠驻留巨噬细胞中富集。流式细胞术数据还表明，在大鼠和人类肾脏组织中存在一个定义明确的固有免疫细胞群体，共同表达 CD74 和 Cd81，提示在多种物种中存在肾脏驻留巨噬细胞。
基于转录特征，我们的数据表明，在多个物种中存在一个保守的固有免疫细胞群体，在小鼠中被定义为驻留巨噬细胞。此外，我们鉴定了潜在的细胞表面标记物，以允许在未来的研究中识别和表征小鼠、大鼠和猪翻译研究中的候选驻留巨噬细胞群体。
