Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002 Jiangsu, China.
J Immunol Res. 2021 Nov 20;2021:1260140. doi: 10.1155/2021/1260140. eCollection 2021.
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.
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.
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 TCR. Macrophages expressed a characteristic panel of markers with varied expression levels including MHC II, SIRP, CD11c, Siglec-F, F4/80, CD64, and CD11b, indicating more subtle differences in marker expression than T cells. The SIRT3/CaOx and SIRT3/CaOx groups exhibited global differences in the intrarenal immune landscape, whereas only small differences existed between the SIRT3/CaOx and SIRT3/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.
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.
肾结石是一种常见的泌尿系统疾病，复发率高，其形成可能与 CaOx 有关，并会引起强烈的免疫反应。我们构建了基于 CyTOF 的肾结石模型免疫图谱，以了解免疫系统如何参与并受 SIRT3 敲除和 CaOx 诱导引起的潜在反应的影响。
我们对肾结石模型中的免疫细胞丰度进行了大规模的 CyTOF 分析。免疫表型数据来自四个不同的小鼠模型，包括 SIRT3 野生型或敲除型，包括和不包括 CaOx 诱导。无监督分析策略，如 SPADE 和 viSNE，揭示了 SIRT3 敲除和 CaOx 诱导肾损伤引起的肾固有免疫成分和免疫改变。
免疫景观全景分析确定 T 细胞和巨噬细胞为肾结石模型中的主要免疫细胞群。CD4 和 CD8 T 细胞亚群表现出高度相似的表型，包括表达 Ki67、Ly6C、Siglec-F 和 TCR 的细胞。巨噬细胞表达特征性标记物面板，其表达水平不同，包括 MHC II、SIRP、CD11c、Siglec-F、F4/80、CD64 和 CD11b，表明与 T 细胞相比，标记物表达存在更细微的差异。SIRT3/CaOx 和 SIRT3/CaOx 组的肾内免疫景观存在全局差异，而 SIRT3/CaOx 和 SIRT3/Ctrl 组之间仅存在微小差异。在主要免疫谱系中，CD4 T 细胞、NK 细胞、单核细胞和 M1 对 CaOx 诱导的反应受 SIRT3 表达调节，而 B 细胞、DC 和粒细胞的表达变化则由 CaOx 诱导引起。受 CaOx 诱导影响的免疫标记物面板随 SIRT3 敲除而显著变化。
在 CaOx 诱导的肾结石模型中，SIRT3 在调节免疫系统方面起着关键作用，特别是在减轻炎症损伤方面。改变的免疫簇和标记物的特征面板提供了新的见解，有助于改善肾结石的预测和管理。
