064 Functional interrogation of lymphocyte subsets in alopecia areata using single-cell RNA sequencing

CD8型 免疫学 发病机制 免疫系统 细胞毒性T细胞 T细胞 效应器 T淋巴细胞 生物 淋巴细胞 斑秃 医学 体外 遗传学
作者
E.Y. Lee,Zhijun Dai,E. Wang,A.M. Christiano
出处
期刊:Journal of Investigative Dermatology [Elsevier BV]
卷期号:142 (8): S11-S11
标识
DOI:10.1016/j.jid.2022.05.118
摘要

Alopecia areata (AA) is one of the most prevalent autoimmune diseases, yet the development of innovative therapeutic strategies has been hampered by an incomplete understanding of disease pathogenesis, such as the complex immunological mechanisms that underlie AA pathogenesis. Here, we performed single-cell RNA sequencing (scRNAseq) of skin-infiltrating immune cells from the well-established graft-induced C3H/HeJ mouse model of AA, together with antibody-based depletion experiments to systematically interrogate the role of specific immune cell types in disease pathophysiology in vivo. Since AA is a predominantly T cell-mediated disease, we focused on dissecting the function of lymphocyte subsets in AA. Both our scRNAseq and functional studies established that CD8+ T cells, whose depletion was sufficient for both disease prevention and reversal, are the main disease-driving cell type in AA. Focused computational analyses of CD8+ T cells identified five CD8+ T cell subsets, ranging from naïve cells to effector and resident T cell populations. CD8+ T cell heterogeneity in AA was defined by an ‘effectorness gradient’ in which CD8+ T cells formed a continuum of interrelated transcriptional states that culminated in increased effector function and tissue residency, as opposed to discrete mutually exclusive populations. Our findings also confirmed a role for CD4+ T helper cells in disease initiation and demonstrated that regulatory T cells are protective against AA. Depletion of natural killer cells, B cells, and γδ T cells had no effect on disease prevention or reversal. Guided by our scRNAseq analyses, we performed a highly comprehensive, systematic interrogation of lymphocyte heterogeneity in AA, and uncovered a novel ‘effectorness gradient’ framework for AA-associated CD8+ T cells with implications for the design of future therapeutics.
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
研友_VZG7GZ应助小呱采纳,获得10
刚刚
1秒前
刘人英完成签到,获得积分10
2秒前
caixukun发布了新的文献求助10
2秒前
归尘发布了新的文献求助10
2秒前
李双兔发布了新的文献求助30
2秒前
蓝橙发布了新的文献求助10
3秒前
4秒前
阿州完成签到,获得积分10
4秒前
4秒前
清新的马里奥完成签到 ,获得积分10
4秒前
张烤明完成签到,获得积分10
5秒前
清爽乐菱完成签到,获得积分10
5秒前
YANG完成签到,获得积分10
5秒前
6秒前
6秒前
大模型应助爱撒娇的紫菜采纳,获得10
6秒前
8秒前
在喝咖啡ing完成签到,获得积分10
10秒前
SL发布了新的文献求助10
10秒前
风清扬应助海东来采纳,获得50
11秒前
灵魂发布了新的文献求助10
11秒前
阿朱发布了新的文献求助10
11秒前
12秒前
drfwjuikesv应助Hangerli采纳,获得10
14秒前
Ava应助泡泡糖与一世安采纳,获得30
15秒前
15秒前
15秒前
15秒前
zhangxu完成签到,获得积分10
17秒前
17秒前
18秒前
22222发布了新的文献求助10
19秒前
19秒前
rpe发布了新的文献求助10
20秒前
hbhb发布了新的文献求助10
21秒前
小嘎完成签到 ,获得积分10
22秒前
Kuta完成签到,获得积分10
22秒前
blue完成签到,获得积分10
24秒前
zhangxu发布了新的文献求助10
24秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
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 3975458
求助须知:如何正确求助?哪些是违规求助? 3519866
关于积分的说明 11199996
捐赠科研通 3256213
什么是DOI,文献DOI怎么找? 1798133
邀请新用户注册赠送积分活动 877386
科研通“疑难数据库(出版商)”最低求助积分说明 806305