纤维化
免疫系统
急性肾损伤
肾
再生(生物学)
生物
癌症研究
人口
下调和上调
细胞生物学
医学
免疫学
病理
基因
内科学
内分泌学
遗传学
环境卫生
作者
Fernanda do Valle Durães,Armelle Lafont,Martin Beibel,Kea Martin,Katy Darribat,Rachel Cuttat,Annick Waldt,Ulrike Naumann,Grazyna Wieczorek,Swann Gaulis,Sabina Pfister,Kirsten D. Mertz,Jianping Li,Guglielmo Roma,Max Warncke
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2020-02-13
卷期号:5 (3)
被引量:74
标识
DOI:10.1172/jci.insight.130651
摘要
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.
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