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

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, th...

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Autores principales:	Wei Zhang, Ling Li, Ti Zhang, Xiaomin Gao, Zeyu Wang, Shaoxiong Ming, Ziyu Fang, Min Liu, Hao Dong, Baoyi Zhu, Junhao Liao, Jianwen Zeng, Yonghan Peng, Xaiofeng Gao
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/7a5c3800b12d4701b564f6cbd03a1ed2
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spelling	oai:doaj.org-article:7a5c3800b12d4701b564f6cbd03a1ed22021-11-29T00:55:54ZAn Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury2314-715610.1155/2021/1260140https://doaj.org/article/7a5c3800b12d4701b564f6cbd03a1ed22021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/1260140https://doaj.org/toc/2314-7156Background. 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.Wei ZhangLing LiTi ZhangXiaomin GaoZeyu WangShaoxiong MingZiyu FangMin LiuHao DongBaoyi ZhuJunhao LiaoJianwen ZengYonghan PengXaiofeng GaoHindawi LimitedarticleImmunologic diseases. AllergyRC581-607ENJournal of Immunology Research, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607
spellingShingle	Immunologic diseases. Allergy RC581-607 Wei Zhang Ling Li Ti Zhang Xiaomin Gao Zeyu Wang Shaoxiong Ming Ziyu Fang Min Liu Hao Dong Baoyi Zhu Junhao Liao Jianwen Zeng Yonghan Peng Xaiofeng Gao An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury
description	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.
format	article
author	Wei Zhang Ling Li Ti Zhang Xiaomin Gao Zeyu Wang Shaoxiong Ming Ziyu Fang Min Liu Hao Dong Baoyi Zhu Junhao Liao Jianwen Zeng Yonghan Peng Xaiofeng Gao
author_facet	Wei Zhang Ling Li Ti Zhang Xiaomin Gao Zeyu Wang Shaoxiong Ming Ziyu Fang Min Liu Hao Dong Baoyi Zhu Junhao Liao Jianwen Zeng Yonghan Peng Xaiofeng Gao
author_sort	Wei Zhang
title	An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury
title_short	An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury
title_full	An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury
title_fullStr	An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury
title_full_unstemmed	An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury
title_sort	immune atlas of nephrolithiasis: single-cell mass cytometry on sirt3 knockout and calcium oxalate-induced renal injury
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/7a5c3800b12d4701b564f6cbd03a1ed2
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An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury

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