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Spatiotemporal immune zonation of the human kidney

Lookup NU author(s): Dr Rachel Botting, Dr Dorin-Mirel Popescu, Dr Roser Vento-Tormo, Emily Stephenson, Dr Kile GreenORCiD, Professor Andrew FilbyORCiD, Dr Steven LisgoORCiD, Emerita Professor Susan Lindsay, Professor Muzlifah Haniffa

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for the Advancement of Science, 2019.

For re-use rights please refer to the publisher's terms and conditions.


Abstract

Copyright © 2019 The Authors.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.


Publication metadata

Author(s): Stewart BJ, Ferdinand JR, Young MD, Mitchell TJ, Loudon KW, Riding AM, Richoz N, Frazer GL, Staniforth JUL, Braga FAV, Botting RA, Popescu D-M, Vento-Tormo R, Stephenson E, Cagan A, Farndon SJ, Polanski K, Efremova M, Green K, Velasco-Herrera MDC, Guzzo C, Collord G, Mamanova L, Aho T, Armitage JN, Riddick ACP, Mushtaq I, Farrell S, Rampling D, Nicholson J, Filby A, Burge J, Lisgo S, Lindsay S, Bajenoff M, Warren AY, Stewart GD, Sebire N, Coleman N, Haniffa M, Teichmann SA, Behjati S, Clatworthy MR

Publication type: Article

Publication status: Published

Journal: Science

Year: 2019

Volume: 365

Issue: 6460

Pages: 1461-1466

Print publication date: 27/09/2019

Online publication date: 04/09/2019

Acceptance date: 04/09/2019

Date deposited: 28/10/2019

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Association for the Advancement of Science

URL: https://doi.org/10.1126/science.aat5031

DOI: 10.1126/science.aat5031


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