An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury

Journal of Immunology Research

Ling Li¹  Wei Zhang¹  Shaoxiong Ming¹  Yonghan Peng¹  Xaiofeng Gao¹  Zeyu Wang¹  Xiaomin Gao¹  Min Liu¹  Ziyu Fang¹  Hao Dong¹  Jianwen Zeng²  Baoyi Zhu²  Junhao Liao²  Ti Zhang³ 

[1] Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China, smmu.edu.cn;Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518 Guangdong, China, gzhmc.edu.cn;National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002 Jiangsu, China, njmu.edu.cn;

DOI  :  10.1155/2021/1260140

来源: Hindawi Publishing Corporation

【 摘 要 】

Background. As a common urological disease with a high recurrence rate, nephrolithiasis caused by CaOx may elicit a strong immunologic response. We present a CyTOF-based atlas of the immune landscape in nephrolithiasis models to understand how the immune system contributes to, and is affected by, the underlying response caused by SIRT3 knockout and CaOx inducement. Materials and Methods. We performed a large-scale CyTOF analysis of immune cell abundance profiles in nephrolithiasis. The immunophenotyping data were collected from four different mouse models, including the SIRT3 wild-type or knockout, including and excluding CaOx inducement. Unsupervised analysis strategies, such as SPADE and viSNE, revealed the intrarenal resident immune components and the immune alterations caused by SIRT3 knockout and CaOx-induced renal injury. Results. An overview analysis of the immune landscape identified T cells and macrophages as the main immune cell population in nephrolithiasis models. Highly similar phenotypes were observed among CD4+ and CD8+ T cell subsets, including cells expressing Ki67, Ly6C, Siglec-F, and TCRβ. Macrophages expressed a characteristic panel of markers with varied expression levels including MHC II, SIRPα, CD11c, Siglec-F, F4/80, CD64, and CD11b, indicating more subtle differences in marker expression than T cells. The SIRT3KO/CaOx and SIRT3WT/CaOx groups exhibited global differences in the intrarenal immune landscape, whereas only small differences existed between the SIRT3KO/CaOx and SIRT3KO/Ctrl groups. Among the major immune lineages, the response of CD4+ T cells, NK cells, monocytes, and M1 to CaOx inducement was regulated by SIRT3 expression in contrast to the expression changes of B cells, DCs, and granulocytes caused by CaOx inducement. The panel of immune markers influenced by CaOx inducement significantly varied with and without SIRT3 knockout. Conclusion. In a CaOx-induced nephrolithiasis model, SIRT3 has a critical role in regulating the immune system, especially in reducing inflammatory injury. The characteristic panel of altered immune clusters and markers provides novel insights leading to improved prediction and management of nephrolithiasis.

【 授权许可】

CC BY