Spatiotemporal immune zonation of the human kidney

Tissue-resident immunecells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immunecells. We used single-cell RNA sequencing to resolve the spatiotemporal immunetopology of the human kidney. We reveal anatomically defined expression patterns of immunegenes within the epithelial compartment, with antimicrobial peptidetranscripts evident in pelvic epithelium in the mature, but not fetal, kidney. A network of tissue-resident myeloid and lymphoid immunecells was evident in both fetal and mature kidney, with postnatal acquisition of transcriptional programs that promote infection-defense capabilities. Epithelial- immunecross-talk orchestrated localization of antibacterial macrophages and neutrophils to the regions of the kidneymost susceptible to infection. Overall, our study provides a global overview of how the immunelandscape of the human kidneyis zonated to counter the dominant immunological challenge.