Altered immune cell phenotypes within chronically ischemic human kidneys distal to occlusive renal artery diseaseXiang-Yang Zhu, Nattawat Klomjit, Aditya S. Pawar, Amrutesh S. Puranik, Zhi-Zhang Yang, Esther Lutgens, Alfonso Eirin, Amir Lerman, Stephen C. Textor, Lilach O. Lerman
Background: Renal artery stenosis (RAS) is a major cause of ischemic kidney disease, which is largely mediated by inflammation. Mapping the immune cell composition in ischemic kidneys might provide useful insight into the disease pathogenesis and uncover therapeutic targets. Methods: We used mass-cytometry (CyTOF) to explore the single-cell composition in a unique dataset of human kidneys nephrectomized due to chronic occlusive vascular disease (RAS, n=3), relatively healthy donor kidneys (n=6), and unaffected sections of kidneys with renal cell carcinoma (RCC, n=3). Renal fibrosis and certain macrophage populations were also evaluated in renal sections. Results: Cytobank analysis showed in RAS kidneys decreased cell populations expressing epithelial markers (CD45-/CD13+) and increased CD45+ inflammatory cells, whereas scattered-tubular-progenitor-like cells (CD45-/CD133+/CD24+) increased compared with kidney donors. Macrophages switched to pro-inflammatory phenotypes in RAS, and the numbers of IL-10-producing dendritic cells (DC) were also lower. Compared with kidney donors, RAS kidneys had decreased overall DC populations, but increased plasmacytoid DC. Furthermore, senescent active T-cells (CD45+/CD28+/CD57+), aged-neutrophils (CD45+/CD15+/CD24+/CD11c+), and regulatory B-cells (CD45+/CD14-/CD24+/CD44+) were increased in RAS. RCC kidneys showed a distribution of cell phenotypes comparable to RAS but less pronounced, accompanied by an increase in CD34+, CD370+, CD103+, and CD11c+/CD103+ cells. Histologically, RAS kidneys showed significantly increased fibrosis and decreased CD163+/CD141+ cells. Conclusion: The single-cell platform CyTOF enables detection of significant changes in renal cells, especially in subsets of immune cells in ischemic human kidneys. Endogenous pro-repair cell types in RAS warrant future study for potential immune therapy.