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Immune cell landscaping reveals a protective role for regulatory T cells during kidney injury and fibrosis

Do Valle Duraes, Fernanda and Lafont, Armelle and Darribat, Katy and Martin, Kea and Cuttat-Theurillat, Rachel and Waldt, Annick and Naumann, Ulrike and Wieczorek, Grazyna and Gaulis, Swann and Pfister, Sabina and Beibel, Martin and Li, Jianping and Roma, Guglielmo and Warncke, Max and Mertz, Kirsten (2020) Immune cell landscaping reveals a protective role for regulatory T cells during kidney injury and fibrosis. JCI insight, 5 (3). ISSN 23793708

Abstract

Acute kidney injury (AKI) and chronic kidney diseases are associated with high mortality and morbidity. Although the underlying mechanisms determining the transition from acute to chronic injury are not completely understood, immune-mediated processes are critical in renal injury. We have performed a comparison of 2 mouse models leading to either kidney regeneration or fibrosis. Using global gene expression profiling we could identify immune-related pathways accounting for the majority of the observed transcriptional changes during fibrosis. Unbiased examination of the immune cell composition, using single-cell RNA sequencing, revealed major changes in tissue-resident macrophages and T cells. Following injury, there was a marked increase in tissue-resident IL-33R+ and IL-2Ra+ regulatory T cells (Tregs). Expansion of this population before injury protected the kidney from injury and fibrosis. Transcriptional profiling of Tregs showed a differential upregulation of regenerative and proangiogenic pathways during regeneration, whereas in the fibrotic environment they expressed markers of hyperactivation and fibrosis. Our data point to a hitherto underappreciated plasticity in Treg function within the same tissue, dictated by environmental cues. Overall, we provide a detailed cellular and molecular characterization of the immunological changes during kidney injury, regeneration, and fibrosis.

Item Type: Article
Keywords: Adaptive immunity Chronic kidney disease Fibrosis Immunology Nephrology
Date Deposited: 05 Mar 2020 00:45
Last Modified: 05 Mar 2020 00:45
URI: https://oak.novartis.com/id/eprint/40046

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