BMSC外泌体传递JKAP，通过AKT/ERK恢复Th17/Treg平衡，缓解类风湿关节炎

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-06 DOI:10.1016/j.isci.2025.112832

Fang-Tian Xu , Yu Ling , Hui-Xian Wei , Lingzhang Meng , Dong Yin , Zhong-Hong Lai , Yu Huang , Xiao Huang , Hai-Ye Li , Qin-Wen Luo , Jian Song , Qiang Tang , Hong-Mian Li

{"title":"BMSC外泌体传递JKAP，通过AKT/ERK恢复Th17/Treg平衡，缓解类风湿关节炎","authors":"Fang-Tian Xu , Yu Ling , Hui-Xian Wei , Lingzhang Meng , Dong Yin , Zhong-Hong Lai , Yu Huang , Xiao Huang , Hai-Ye Li , Qin-Wen Luo , Jian Song , Qiang Tang , Hong-Mian Li","doi":"10.1016/j.isci.2025.112832","DOIUrl":null,"url":null,"abstract":"<div><div>JKAP regulates T cell immunity and inflammation in autoimmune diseases. This study investigates how bone marrow mesenchymal stem cell (BMSC)-derived exosomes deliver JKAP to restore Th17/Treg balance in rheumatoid arthritis (RA). RA CD4<sup>+</sup> T-cells and fibroblast-like synoviocytes (RA-FLS) were treated with BMSC, exosomes, or JKAP-modified exosomes ± AKT/ERK inhibitors. BMSC/exosomes suppressed Th17 and promoted Treg differentiation, effects diminished without exosomes. JKAP knockdown impaired exosome-mediated Th17/Treg regulation and AKT/ERK activation, while overexpression enhanced these effects. JKAP-deficient exosomes increased CD4<sup>+</sup> T cell proliferation and RA-FLS inflammation, reversed by AKT/ERK inhibition. In collagen-induced arthritis mice, exosomes alleviated symptoms and restored Th17/Treg balance, whereas JKAP knockdown exacerbated arthritis and disrupted balance. JKAP-overexpressing exosomes showed opposite effects. Thus, BMSC exosomes mitigate RA by delivering JKAP to restore immune balance via AKT/ERK pathways.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112832"},"PeriodicalIF":4.6000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis\",\"authors\":\"Fang-Tian Xu , Yu Ling , Hui-Xian Wei , Lingzhang Meng , Dong Yin , Zhong-Hong Lai , Yu Huang , Xiao Huang , Hai-Ye Li , Qin-Wen Luo , Jian Song , Qiang Tang , Hong-Mian Li\",\"doi\":\"10.1016/j.isci.2025.112832\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>JKAP regulates T cell immunity and inflammation in autoimmune diseases. This study investigates how bone marrow mesenchymal stem cell (BMSC)-derived exosomes deliver JKAP to restore Th17/Treg balance in rheumatoid arthritis (RA). RA CD4<sup>+</sup> T-cells and fibroblast-like synoviocytes (RA-FLS) were treated with BMSC, exosomes, or JKAP-modified exosomes ± AKT/ERK inhibitors. BMSC/exosomes suppressed Th17 and promoted Treg differentiation, effects diminished without exosomes. JKAP knockdown impaired exosome-mediated Th17/Treg regulation and AKT/ERK activation, while overexpression enhanced these effects. JKAP-deficient exosomes increased CD4<sup>+</sup> T cell proliferation and RA-FLS inflammation, reversed by AKT/ERK inhibition. In collagen-induced arthritis mice, exosomes alleviated symptoms and restored Th17/Treg balance, whereas JKAP knockdown exacerbated arthritis and disrupted balance. JKAP-overexpressing exosomes showed opposite effects. Thus, BMSC exosomes mitigate RA by delivering JKAP to restore immune balance via AKT/ERK pathways.</div></div>\",\"PeriodicalId\":342,\"journal\":{\"name\":\"iScience\",\"volume\":\"28 7\",\"pages\":\"Article 112832\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"iScience\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2589004225010934\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589004225010934","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

JKAP调节自身免疫性疾病中的T细胞免疫和炎症。本研究探讨骨髓间充质干细胞（BMSC）衍生的外泌体如何递送JKAP以恢复类风湿关节炎（RA）中Th17/Treg的平衡。用BMSC、外泌体或jkap修饰的外泌体±AKT/ERK抑制剂治疗RA CD4+ t细胞和成纤维细胞样滑膜细胞（RA- fls）。BMSC/外泌体抑制Th17并促进Treg分化，没有外泌体的作用减弱。JKAP敲除会损害外泌体介导的Th17/Treg调节和AKT/ERK激活，而过表达会增强这些作用。jakap缺陷外泌体增加CD4+ T细胞增殖和RA-FLS炎症，AKT/ERK抑制逆转。在胶原诱导的关节炎小鼠中，外泌体缓解了症状并恢复了Th17/Treg平衡，而JKAP敲低则加重了关节炎并破坏了平衡。过表达jkap的外泌体表现出相反的效果。因此，BMSC外泌体通过AKT/ERK通路传递JKAP来恢复免疫平衡，从而减轻RA。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis

查看原文本刊更多论文

BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis

JKAP regulates T cell immunity and inflammation in autoimmune diseases. This study investigates how bone marrow mesenchymal stem cell (BMSC)-derived exosomes deliver JKAP to restore Th17/Treg balance in rheumatoid arthritis (RA). RA CD4⁺ T-cells and fibroblast-like synoviocytes (RA-FLS) were treated with BMSC, exosomes, or JKAP-modified exosomes ± AKT/ERK inhibitors. BMSC/exosomes suppressed Th17 and promoted Treg differentiation, effects diminished without exosomes. JKAP knockdown impaired exosome-mediated Th17/Treg regulation and AKT/ERK activation, while overexpression enhanced these effects. JKAP-deficient exosomes increased CD4⁺ T cell proliferation and RA-FLS inflammation, reversed by AKT/ERK inhibition. In collagen-induced arthritis mice, exosomes alleviated symptoms and restored Th17/Treg balance, whereas JKAP knockdown exacerbated arthritis and disrupted balance. JKAP-overexpressing exosomes showed opposite effects. Thus, BMSC exosomes mitigate RA by delivering JKAP to restore immune balance via AKT/ERK pathways.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.