Dysregulated Treg repair responses lead to chronic rejection after heart transplantation

移植 医学 心脏移植 免疫学 移植物排斥 铅(地质) 生物 内科学 古生物学
作者
Jordan Warunek,Lu Fan,Xue Zhang,Sihua Wang,Steven M. Sanders,Tengfang Li,Lisa Mathews,Gaelen K. Dwyer,Michelle A. Wood,Stephanie Traczek,Andrew Lesniak,Kassandra Baron,H. Trent Spencer,Johnny Bou Saba,Emmanuel León Colón,Tracy Tabib,Robert Lafyatis,Mark A. Ross,Anthony J. Demetris,Simon C. Watkins
出处
期刊:Journal of Clinical Investigation [American Society for Clinical Investigation]
卷期号:134 (23) 被引量:2
标识
DOI:10.1172/jci173593
摘要

Chronic rejection (CR) after organ transplantation is alloimmune injury manifested by graft vascular remodeling and fibrosis that is resistant to immunosuppression. Single-cell RNA-Seq analysis of MHC class II-mismatched (MHCII-mismatched) heart transplants developing chronic rejection identified graft IL-33 as a stimulator of tissue repair pathways in infiltrating macrophages and Tregs. Using IL-33-deficient donor mice, we show that graft fibroblast-derived IL-33 potently induced amphiregulin (Areg) expression by recipient Tregs. The assessment of clinical samples also confirmed increased expression of Areg by intragraft Tregs also during rejection. Areg is an EGF secreted by multiple immune cells to shape immunomodulation and tissue repair. In particular, Areg is proposed to play a major role in Treg-mediated muscle, epithelium, and nerve repair. Assessment of recipient mice with Treg-specific deletion of Areg surprisingly uncovered that Treg secretion of Areg contributed to CR. Specifically, heart transplants from recipients with Areg-deficient Tregs showed less fibrosis, vasculopathy, and vessel-associated fibrotic niches populated by recipient T cells. Mechanistically, we show that Treg-secreted Areg functioned to increase fibroblast proliferation. In total, these studies identify how a dysregulated repair response involving interactions between IL-33+ fibroblasts in the allograft and recipient Tregs contributed to the progression of CR.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
烟花应助qq采纳,获得10
1秒前
monoklatt发布了新的文献求助10
1秒前
2秒前
2秒前
研友_84mlkL发布了新的文献求助10
2秒前
4秒前
文献达人发布了新的文献求助10
5秒前
小蘑菇应助吃吃采纳,获得10
6秒前
6秒前
彭于晏应助zs采纳,获得10
7秒前
桥豆麻袋发布了新的文献求助10
7秒前
8秒前
9秒前
赵嘉钰完成签到,获得积分10
11秒前
SYLH应助研友_LNVX1L采纳,获得10
12秒前
复杂的兔子完成签到,获得积分10
12秒前
论文顺利完成签到,获得积分10
12秒前
lii应助上官靖采纳,获得10
13秒前
qq发布了新的文献求助10
14秒前
还好还好发布了新的文献求助10
14秒前
14秒前
15秒前
改论文不看剧完成签到,获得积分10
15秒前
搜集达人应助1234采纳,获得10
15秒前
zs完成签到,获得积分10
17秒前
都好都好好的完成签到,获得积分10
18秒前
19秒前
处处铃铛响完成签到,获得积分10
19秒前
量子星尘发布了新的文献求助10
19秒前
俗丨发布了新的文献求助10
19秒前
论文顺利发布了新的文献求助10
20秒前
zs发布了新的文献求助10
20秒前
李健应助科研通管家采纳,获得30
20秒前
QUA应助科研通管家采纳,获得10
20秒前
沐青应助科研通管家采纳,获得60
20秒前
小蘑菇应助科研通管家采纳,获得10
20秒前
乐观小之应助科研通管家采纳,获得10
21秒前
21秒前
汉堡包应助科研通管家采纳,获得10
21秒前
情怀应助科研通管家采纳,获得10
21秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance 500
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969940
求助须知:如何正确求助?哪些是违规求助? 3514642
关于积分的说明 11175298
捐赠科研通 3249947
什么是DOI,文献DOI怎么找? 1795178
邀请新用户注册赠送积分活动 875617
科研通“疑难数据库(出版商)”最低求助积分说明 804891