ATF4 drives regulatory T cell functional specification in homeostasis and obesity

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2025-03-14 DOI:10.1126/sciimmunol.adp7193

Ke Wang, Andrea Farrell, Enchen Zhou, Houji Qin, Zixuan Zeng, Kailun Zhou, Karina Cunha e Rocha, Dinghong Zhang, Gaowei Wang, Amha Atakilit, Dean Sheppard, Li-Fan Lu, Chunyu Jin, Wei Ying

{"title":"ATF4 drives regulatory T cell functional specification in homeostasis and obesity","authors":"Ke Wang, Andrea Farrell, Enchen Zhou, Houji Qin, Zixuan Zeng, Kailun Zhou, Karina Cunha e Rocha, Dinghong Zhang, Gaowei Wang, Amha Atakilit, Dean Sheppard, Li-Fan Lu, Chunyu Jin, Wei Ying","doi":"10.1126/sciimmunol.adp7193","DOIUrl":null,"url":null,"abstract":"Regulatory T cells (T regs ) have diverse functional specification in homeostasis and disease. However, how liver T regs function and are transcriptionally regulated in obesity is not well understood. Here, we identified that effector T regs expressing activating transcription factor 4 (ATF4) were enriched in the livers of obese mice. ATF4 was critical for driving an effector T reg transcriptional program, and ATF4-expressing T regs promoted the development of obesity-induced liver fibrosis by enhancing transforming growth factor–β activation via integrin αvβ8. T reg -specific deletion of Atf4 resulted in reduced liver T regs and attenuation of obesity-induced liver abnormalities. Furthermore, ATF4 was required to promote the differentiation of nonlymphoid tissue T reg precursors under steady state. These findings demonstrate that ATF4 is important for regulating T reg functional specification in homeostasis and obesity.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"5 1","pages":""},"PeriodicalIF":17.6000,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1126/sciimmunol.adp7193","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Regulatory T cells (T regs ) have diverse functional specification in homeostasis and disease. However, how liver T regs function and are transcriptionally regulated in obesity is not well understood. Here, we identified that effector T regs expressing activating transcription factor 4 (ATF4) were enriched in the livers of obese mice. ATF4 was critical for driving an effector T reg transcriptional program, and ATF4-expressing T regs promoted the development of obesity-induced liver fibrosis by enhancing transforming growth factor–β activation via integrin αvβ8. T reg -specific deletion of Atf4 resulted in reduced liver T regs and attenuation of obesity-induced liver abnormalities. Furthermore, ATF4 was required to promote the differentiation of nonlymphoid tissue T reg precursors under steady state. These findings demonstrate that ATF4 is important for regulating T reg functional specification in homeostasis and obesity.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.