Wei Jiang, Tao-Tao Tang, Yi-Lin Zhang, Zuo-Lin Li, Yi Wen, Qin Yang, Yu-Qi Fu, Jing Song, Qiu-Li Wu, Min Wu, Bin Wang, Bi-Cheng Liu, Lin-Li Lv
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引用次数: 0
Abstract
Acute kidney injury (AKI) transformed to chronic kidney disease (CKD) is a critical clinical issue characterized by tubulointerstitial inflammation (TII) and fibrosis. However, the exact mechanism remains largely unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to obtain a high-resolution profile of T cells in AKI to CKD transition with a mice model of unilateral ischemia-reperfusion injury (uIRI). We found that T cells accumulated increasingly with the progression of AKI to CKD, which was categorized into 9 clusters. A notably increased proportion of CD8 T cells via self-proliferation occurred in the early stage of AKI was identified. Further study revealed that the CD8 T cells were recruited through CXCL16-CXCR6 pathway mediated by macrophages. Notably, CD8 T cells induced endothelial cell apoptosis via Fas ligand-Fas signaling. Consistently, increased CD8 T cell infiltration accompanied with peritubular capillaries (PTCs) rarefaction was observed in uIRI mice. More impressively, the loss of PTCs and renal fibrosis was remarkably ameliorated after the elimination of CD8 T cells. In summary, our study provides a novel insight into the role of CD8 T cells in the transition from AKI to CKD via induction of PTCs rarefaction, which could suggest a promising therapeutic target for AKI.
急性肾损伤(AKI)转化为慢性肾病(CKD)是一个关键的临床问题,其特点是肾小管间质炎症(TII)和纤维化。然而,其确切机制在很大程度上仍不清楚。在这项研究中,我们利用单细胞 RNA 测序(scRNA-seq)技术,通过单侧缺血再灌注损伤(uIRI)小鼠模型获得了从 AKI 向 CKD 转化过程中 T 细胞的高分辨率图谱。我们发现,随着 AKI 向 CKD 的进展,T 细胞的积累也越来越多,可分为 9 个集群。在 AKI 早期,CD8 T 细胞通过自我增殖的比例明显增加。进一步研究发现,CD8 T 细胞是通过巨噬细胞介导的 CXCL16-CXCR6 通路被招募的。值得注意的是,CD8 T 细胞通过 Fas 配体-Fas 信号诱导内皮细胞凋亡。同样,在uIRI小鼠中观察到CD8 T细胞浸润增加,同时伴有管周毛细血管(PTC)稀疏。更令人印象深刻的是,在消除 CD8 T 细胞后,PTCs 的丧失和肾脏纤维化明显改善。总之,我们的研究通过诱导PTCs稀疏化,对CD8 T细胞在AKI向CKD转变过程中的作用提供了新的见解,这可能是治疗AKI的一个有前途的靶点。
期刊介绍:
The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.