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

Abstract

Acute kidney injury (AKI) and chronic kidney diseases (CKD) are associated with high mortality and morbidity in hospitalized patients. Although the underlying mechanisms determining the transition from acute to irreversible chronic injury are not well understood, immune mediated inflammatory processes are critical in renal injury. We have performed a comparison of two mouse models leading to either kidney regeneration or fibrosis, to better characterize the cellular and molecular events leading to both outcomes. Global gene expression profiling and histological analysis revealed a major upregulation of immune system related pathways during fibrosis. Further unbiased examination of the immune cell composition, using single-cell RNA sequencing, revealed that tissue resident macrophages and T cells were major altered populations. In fibrotic kidneys, there was a marked increase in tissue resident IL33R+ and IL2Ra+ regulatory T cells (Tregs). Indeed, prophylactic expansion of this population resulted in protection from kidney injury and fibrosis. Transcriptional profiling of Tregs showed a differential up-regulation of regenerative and pro-angiogenic set of genes in the regeneration model, whereas they expressed markers of hyper activation and fibrosis in the fibrosis model. This suggests that Tregs could exert different functions in the same tissue, dictated by environmental cues. Overall, we have provided a detailed cellular and molecular characterization of murine kidneys after injury and identified key changes in immune cell populations during fibrosis development.

Item Type:	Article
Keywords:	Acute kidney injury, Treg, fibrosis, single cell RNAsequecing
Date Deposited:	05 May 2020 00:45
Last Modified:	05 May 2020 00:45
URI:	https://oak.novartis.com/id/eprint/39815