Single-Cell Sequencing Informs That Mesenchymal Stem Cell Alleviates Renal Injury Through Regulating Kidney Regional Immunity in Lupus Nephritis.

IF 2.5 3区医学 Q3 CELL & TISSUE ENGINEERING

Stem cells and development Pub Date : 2023-08-01 DOI:10.1089/scd.2023.0047

Cheng Zhou, Xinlong Bai, Yunzhao Yang, Meihan Shi, Xueyuan Bai

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Abstract

Lupus nephritis (LN) is the common complication of systemic lupus erythematosus. The pathogenesis of LN kidney injury is unclear. In addition to systemic (extrarenal) immune cells, local (intrarenal) immune cells residing in "kidney regional immunity" are momentous in LN. Mesenchymal stem cell (MSC) therapy is effective for LN. However, mechanisms of MSC therapy remains unclear. In this study, we first systematically investigated the effects of MSC on immune cells in kidney regional immunity in LN using single-cell sequencing. We found that MSC reduced proinflammatory central memory CD4⁺ T cells, cytotoxic tissue-resident memory CD8⁺ T cells and exhausted CD8⁺ T cells, increased anti-inflammatory Naive/Effector CD8⁺ T cells and type 1 regulatory T cells; reduced infiltrating proinflammatory Ly6c hi/inter/lo era2⁺ macrophages, increased anti-inflammatory resident macrophage and Ly6c lo ear2^- macrophage; and reduced long-lived plasma cells and proinflammatory neutrophils and dendritic cells. This study laid a foundation for clinical applications of MSC.

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单细胞测序显示间充质干细胞通过调节狼疮性肾炎患者的肾区域免疫减轻肾损伤。

狼疮性肾炎(LN)是系统性红斑狼疮的常见并发症。LN肾损伤的发病机制尚不清楚。除了全身性(肾外)免疫细胞外，存在于“肾区域免疫”中的局部(肾内)免疫细胞在LN中也很重要。间充质干细胞(MSC)治疗LN有效。然而，MSC治疗的机制尚不清楚。在这项研究中，我们首次使用单细胞测序系统地研究了间充质干细胞对LN肾脏区域免疫中免疫细胞的影响。我们发现MSC降低了促炎中枢记忆CD4+ T细胞、细胞毒性组织驻留记忆CD8+ T细胞和耗竭CD8+ T细胞，增加了抗炎初始/效应CD8+ T细胞和1型调节性T细胞;浸润性促炎Ly6c hi/inter/lo era2+巨噬细胞减少，抗炎常驻巨噬细胞和Ly6c lo ear2-巨噬细胞增加;减少了长寿的浆细胞，促炎中性粒细胞和树突状细胞。本研究为MSC的临床应用奠定了基础。

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来源期刊

Stem cells and development 医学-细胞与组织工程

CiteScore

7.80

自引率

2.50%

发文量

审稿时长

3 months

期刊介绍： Stem Cells and Development is globally recognized as the trusted source for critical, even controversial coverage of emerging hypotheses and novel findings. With a focus on stem cells of all tissue types and their potential therapeutic applications, the Journal provides clinical, basic, and translational scientists with cutting-edge research and findings. Stem Cells and Development coverage includes: Embryogenesis and adult counterparts of this process Physical processes linking stem cells, primary cell function, and structural development Hypotheses exploring the relationship between genotype and phenotype Development of vasculature, CNS, and other germ layer development and defects Pluripotentiality of embryonic and somatic stem cells The role of genetic and epigenetic factors in development