Spatiotemporal immune zonation of the human kidney.
Frazer, Gordon L
Armitage, James N
Riddick, Antony CP
Science (New York, N.Y.)
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Stewart, B. J., Ferdinand, J., Young, M. D., Mitchell, T., Loudon, K. W., Riding, A. M., Richoz, N., et al. (2019). Spatiotemporal immune zonation of the human kidney.. Science (New York, N.Y.), 365 (6460), 1461-1466. https://doi.org/10.1126/science.aat5031
Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly, or via crosstalk with immune cells. We used single cell RNA sequencing to resolve the spatio-temporal immune topology of the human kidney. We reveal anatomically-defined expression patterns of immune genes within the epithelial compartment, with anti-microbial 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 post-natal acquisition of transcriptional programs that promote infection-defense capabilities. Epithelial-immune crosstalk orchestrated localization of anti-bacterial 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 Program
Arthritis Research UK (21777)
Kidney Research UK (TF_013_20171124)
External DOI: https://doi.org/10.1126/science.aat5031
This record's URL: https://www.repository.cam.ac.uk/handle/1810/297504