`Integrated multi-modal dissection of IVIg-mediated immune reprogramming in lupus mice

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-10-03 DOI:10.1016/j.lfs.2025.123997

Xin Yuan , Pan Sun , Tong Wang , Wei Zhang , Peng Jiang , Hong Liang , Xiaochen Yan , Tiancheng Chu , Xi Du , Shengliang Ye , Li Ma , Ping Fu , Zongkui Wang , Changqing Li

{"title":"`Integrated multi-modal dissection of IVIg-mediated immune reprogramming in lupus mice","authors":"Xin Yuan , Pan Sun , Tong Wang , Wei Zhang , Peng Jiang , Hong Liang , Xiaochen Yan , Tiancheng Chu , Xi Du , Shengliang Ye , Li Ma , Ping Fu , Zongkui Wang , Changqing Li","doi":"10.1016/j.lfs.2025.123997","DOIUrl":null,"url":null,"abstract":"<div><div>Intravenous immunoglobulin (IVIg) is widely used to treat autoimmune diseases, yet its precise mechanisms of action in systemic lupus erythematosus remain incompletely understood. Here, we employed an integrated multi-modal approach combining single-cell RNA sequencing, quantitative proteomics, flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay, and histopathological analysis to investigate IVIg-induced immune reprogramming in MRL/lpr lupus-prone mice. IVIg treatment markedly alleviated disease manifestations, including splenomegaly, proteinuria, renal injury, and systemic autoantibody production. Histological examination of the spleen and kidney showed decreased lymphoid hyperplasia, glomerular inflammation, and tissue damage in IVIg-treated mice. At the immune-cell level, IVIg was associated with alterations in T and B cell activation states, partial restoration of immune repertoire diversity, and shifts in dendritic cell populations. Collectively, our integrated analyses suggest that IVIg treatment is correlated with broad immunomodulatory changes in splenic immune composition in lupus-prone mice.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123997"},"PeriodicalIF":5.1000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320525006332","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Intravenous immunoglobulin (IVIg) is widely used to treat autoimmune diseases, yet its precise mechanisms of action in systemic lupus erythematosus remain incompletely understood. Here, we employed an integrated multi-modal approach combining single-cell RNA sequencing, quantitative proteomics, flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay, and histopathological analysis to investigate IVIg-induced immune reprogramming in MRL/lpr lupus-prone mice. IVIg treatment markedly alleviated disease manifestations, including splenomegaly, proteinuria, renal injury, and systemic autoantibody production. Histological examination of the spleen and kidney showed decreased lymphoid hyperplasia, glomerular inflammation, and tissue damage in IVIg-treated mice. At the immune-cell level, IVIg was associated with alterations in T and B cell activation states, partial restoration of immune repertoire diversity, and shifts in dendritic cell populations. Collectively, our integrated analyses suggest that IVIg treatment is correlated with broad immunomodulatory changes in splenic immune composition in lupus-prone mice.

查看原文本刊更多论文

狼疮小鼠ivig介导的免疫重编程的综合多模态解剖

静脉注射免疫球蛋白（IVIg）被广泛用于治疗自身免疫性疾病，但其在系统性红斑狼疮中的确切作用机制尚不完全清楚。在这里，我们采用综合的多模式方法，结合单细胞RNA测序，定量蛋白质组学，流式细胞术，免疫荧光，酶联免疫吸附测定和组织病理学分析来研究ivig诱导MRL/lpr狼疮易感小鼠的免疫重编程。IVIg治疗显著缓解了疾病的表现，包括脾肿大、蛋白尿、肾损伤和全身自身抗体的产生。脾脏和肾脏的组织学检查显示，ivig处理的小鼠淋巴样增生、肾小球炎症和组织损伤减少。在免疫细胞水平上，IVIg与T细胞和B细胞激活状态的改变、免疫库多样性的部分恢复以及树突状细胞群的变化有关。总的来说，我们的综合分析表明，IVIg治疗与狼疮易感小鼠脾免疫成分的广泛免疫调节变化相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.