Spatiotemporal immune zonation of the human kidney.

Abstract

Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immune cells. We used single-cell RNA sequencing to resolve the spatiotemporal immune topology of the human kidney. We reveal anatomically defined expression patterns of immune genes within the epithelial compartment, with antimicrobial peptide transcripts evident in pelvic epithelium in the mature, but not fetal, kidney. A network of tissue-resident myeloid and lymphoid immune cells was evident in both fetal and mature kidney, with postnatal acquisition of transcriptional programs that promote infection-defense capabilities. Epithelial-immune cross-talk orchestrated localization of antibacterial macrophages and neutrophils to the regions of the kidney most susceptible to infection. Overall, our study provides a global overview of how the immune landscape of the human kidney is zonated to counter the dominant immunological challenge.St Baldrick's Foundation (Robert J Arceci International Award to S.B.). Additional funding was received from the Wellcome Trust (S.B.: 110104/Z/15/Z; M.H.: 107931/Z/15/Z; studentships to B.J.S., G.C., A.M.R., and C.G.). Kidney cancer bio-sampling was funded by core infrastructural funding from the Cambridge Biomedical Research Campus (CBRC) and Cancer Research UK Cambridge Centre. Additional funding in support of individual authors was provided as follows: B.J.S (CRUK predoctoral bursary, C63442/A25230); M.R.C. (CBRC; NIHR Blood and Transplant Research Unit, RG75628; MRC New Investigator Research Grant, MR/N024907/1; Arthritis Research UK Cure Challenge Research Grant, 21777; NIHR Research Professorship RP-2017-08-ST2-002); M.H. (The Lister Institute for Preventative Medicine; NIHR and Newcastle-Biomedical Research Centre); A.F. (ISAC SRL-EL program); S.Lis, S.Lin. (joint Wellcome Trust/MRC, 099175/Z/12/Z); K.W.L (Kidney Research UK Clinical Training Fellowship, TF_013_20171124). R.V-T is supported by an EMBO Long-Term Fellowship and a Human Frontier Science Progra