Effect of Impaired T Cell Receptor Signaling on the Gut Microbiota in a Mouse Model of Systemic Autoimmunity

T细胞受体 肠道菌群 免疫学 自身免疫 免疫系统 生物 失调 T细胞
作者
Mirei Shirakashi,Mikako Maruya,Keiji Hirota,Tatsuaki Tsuruyama,Takashi Matsuo,Ryu Watanabe,Koichi Murata,Masao Tanaka,Hiromu Ito,Hajime Yoshifuji,Koichiro Ohmura,Dirk Elewaut,Shimon Sakaguchi,Sidonia Fagarasan,Tsuneyo Mimori,Motomu Hashimoto
出处
期刊:Arthritis & rheumatology [Wiley]
卷期号:74 (4): 641-653 被引量:31
标识
DOI:10.1002/art.42016
摘要

T cell receptor (TCR) signaling abnormalities and gut dysbiosis are thought to be involved in the development of systemic lupus erythematosus (SLE). However, it is not known whether these mechanisms are interrelated. This study was undertaken to explore the impact of defective TCR signaling on microbiota-driven immune responses and the consequent triggering of systemic autoimmunity.The responses of B6SKG mice harboring a mutation in ZAP-70 leading to spontaneous development of SLE were evaluated under specific pathogen-free (SPF) and germ-free (GF) conditions. The gut microbiome was analyzed using 16S ribosomal RNA sequencing. Secretory IgA production in the gut and follicular helper T (Tfh) cell development in the spleen and Peyer's patches were analyzed. Interleukin-17 (IL-17)-deficient mice and segmented filamentous bacteria (SFB)-specific TCR-transgenic mice were used to examine the role of IL-17 and thymic selection.SLE development in B6SKG mice was significantly more attenuated under GF conditions than under SPF conditions. The gut microbiota in B6SKG mice was altered, which was associated with the expansion of SFB and consequent development of SLE by driving Th17 cell differentiation, which was in turn blunted by IL-17 deficiency. Notably, although systemic Tfh development and autoantibody IgG response were enhanced, local gut Tfh and IgA responses were impaired. Moreover, experiments in SFB-specific TCR-transgenic mice revealed that this differential response was caused by altered thymic selection of self- and microbiota-reactive TCR because of defective TCR signaling.Our findings indicate that defective TCR signaling alters the gut microbiota and promotes systemic autoimmunity by driving Th17 cell differentiation.
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
ECUST完成签到,获得积分10
刚刚
笑点低完成签到,获得积分10
1秒前
酸奶辣条完成签到,获得积分20
2秒前
PXP发布了新的文献求助10
3秒前
ssssxr发布了新的文献求助10
4秒前
欧阳正义发布了新的文献求助10
5秒前
沉淀完成签到 ,获得积分10
5秒前
博修发布了新的文献求助10
5秒前
勤恳的半邪完成签到,获得积分10
5秒前
灯与鬼发布了新的文献求助10
5秒前
8秒前
ZERO完成签到,获得积分10
11秒前
ssssxr完成签到,获得积分20
12秒前
Neko发布了新的文献求助10
13秒前
13秒前
酸奶辣条发布了新的文献求助10
13秒前
18秒前
CodeCraft应助博修采纳,获得10
21秒前
21秒前
xu完成签到 ,获得积分10
21秒前
领导范儿应助PXP采纳,获得10
23秒前
欧阳正义发布了新的文献求助10
26秒前
26秒前
深情安青应助夔kk采纳,获得30
27秒前
xzzt发布了新的文献求助10
27秒前
28秒前
29秒前
安白完成签到 ,获得积分20
31秒前
hoshi发布了新的文献求助10
31秒前
我陈雯雯实名上网完成签到,获得积分10
31秒前
32秒前
PXP发布了新的文献求助10
35秒前
36秒前
37秒前
38秒前
博修发布了新的文献求助10
40秒前
芒芒发布了新的文献求助200
41秒前
41秒前
烟花应助飞天817采纳,获得10
41秒前
41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
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 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 3967279
求助须知:如何正确求助?哪些是违规求助? 3512575
关于积分的说明 11164253
捐赠科研通 3247522
什么是DOI,文献DOI怎么找? 1793850
邀请新用户注册赠送积分活动 874729
科研通“疑难数据库(出版商)”最低求助积分说明 804495