ROS-dependent SOCS3 upregulation disrupts regulatory T cell stability during autoimmune disease development

IF 10.7 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Redox Biology Pub Date : 2025-03-10 DOI:10.1016/j.redox.2025.103590
Hiroki Satooka, Yuzuki Nakamura, Takako Hirata
{"title":"ROS-dependent SOCS3 upregulation disrupts regulatory T cell stability during autoimmune disease development","authors":"Hiroki Satooka,&nbsp;Yuzuki Nakamura,&nbsp;Takako Hirata","doi":"10.1016/j.redox.2025.103590","DOIUrl":null,"url":null,"abstract":"<div><div>Autoimmune diseases including rheumatoid arthritis (RA) are often associated with high levels of reactive oxygen species (ROS); however, the ROS targets in autoimmunity are diverse and unclear. Using collagen-induced arthritis (CIA) mice as a model for RA, we report that antioxidants markedly suppress joint inflammation, antibody production, and effector T cell responses. We found that the frequency of CD4<sup>+</sup> regulatory T cells (Tregs) was reduced in CIA mice, which was reversed by antioxidant treatment, and SOCS3, known to be associated with Treg instability, was upregulated in Tregs from both RA patients and CIA mice. Mechanistically, SOCS3 upregulation was induced by ROS-dependent PTEN oxidation and the resultant Akt/mTOR/STAT3 activation. We further showed that the source of ROS involved in this pathway is NADPH oxidase 2 (Nox2). Nox2 expression was upregulated in Tregs from CIA mice, and Nox2 transduction induced a decrease in Treg frequency that depended on SOCS3 upregulation. This study thus provides a mechanistic understanding of ROS-induced Treg instability and suggests that ROS-dependent disruption of Treg homeostasis underlies the development and progression of autoimmune diseases.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103590"},"PeriodicalIF":10.7000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Redox Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S221323172500103X","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Autoimmune diseases including rheumatoid arthritis (RA) are often associated with high levels of reactive oxygen species (ROS); however, the ROS targets in autoimmunity are diverse and unclear. Using collagen-induced arthritis (CIA) mice as a model for RA, we report that antioxidants markedly suppress joint inflammation, antibody production, and effector T cell responses. We found that the frequency of CD4+ regulatory T cells (Tregs) was reduced in CIA mice, which was reversed by antioxidant treatment, and SOCS3, known to be associated with Treg instability, was upregulated in Tregs from both RA patients and CIA mice. Mechanistically, SOCS3 upregulation was induced by ROS-dependent PTEN oxidation and the resultant Akt/mTOR/STAT3 activation. We further showed that the source of ROS involved in this pathway is NADPH oxidase 2 (Nox2). Nox2 expression was upregulated in Tregs from CIA mice, and Nox2 transduction induced a decrease in Treg frequency that depended on SOCS3 upregulation. This study thus provides a mechanistic understanding of ROS-induced Treg instability and suggests that ROS-dependent disruption of Treg homeostasis underlies the development and progression of autoimmune diseases.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
依赖于 ROS 的 SOCS3 上调破坏了自身免疫性疾病发展过程中调节性 T 细胞的稳定性
包括类风湿性关节炎(RA)在内的自身免疫性疾病通常与高水平的活性氧(ROS)有关;然而,自身免疫中的 ROS 靶点多种多样,尚不清楚。我们利用胶原诱导的关节炎(CIA)小鼠作为类风湿性关节炎的模型,发现抗氧化剂能明显抑制关节炎症、抗体生成和效应 T 细胞反应。我们发现,CD4+调节性T细胞(Tregs)在CIA小鼠中的频率降低,而抗氧化剂治疗可逆转这一现象,并且已知与Treg不稳定性有关的SOCS3在RA患者和CIA小鼠的Tregs中均上调。从机理上讲,SOCS3的上调是由ROS依赖的PTEN氧化和由此导致的Akt/mTOR/STAT3激活诱导的。我们进一步发现,参与这一途径的 ROS 来源是 NADPH 氧化酶 2(Nox2)。Nox2 在 CIA 小鼠的 Tregs 中表达上调,Nox2 转导诱导 Treg 频率的降低取决于 SOCS3 的上调。因此,这项研究提供了对 ROS 诱导的 Treg 不稳定性的机理认识,并表明 ROS 依赖性的 Treg 平衡破坏是自身免疫性疾病发生和发展的基础。
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 去求助
来源期刊
Redox Biology
Redox Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
19.90
自引率
3.50%
发文量
318
审稿时长
25 days
期刊介绍: Redox Biology is the official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe. It is also affiliated with the International Society for Free Radical Research (SFRRI). This journal serves as a platform for publishing pioneering research, innovative methods, and comprehensive review articles in the field of redox biology, encompassing both health and disease. Redox Biology welcomes various forms of contributions, including research articles (short or full communications), methods, mini-reviews, and commentaries. Through its diverse range of published content, Redox Biology aims to foster advancements and insights in the understanding of redox biology and its implications.
期刊最新文献
Viral inactivation of murine coronavirus via multiple gas plasma-derived reactive species ROS-dependent SOCS3 upregulation disrupts regulatory T cell stability during autoimmune disease development Corrigendum to "Deciphering the ferroptosis pathways in dorsal root ganglia of Friedreich ataxia models. The role of LKB1/AMPK, KEAP1, and GSK3β in the impairment of the NRF2 response" [Redox Biol. 76 (2024) 103339]. A high-resolution N-glycoproteome landscape of aging mouse ovary Role of oxidative balance score in staging and mortality risk of cardiovascular-kidney-metabolic syndrome: Insights from traditional and machine learning approaches
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1