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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
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动脉样硬化中的致病性自身免疫源自最初保护性阿波蛋白B100-反应性CD4+ T-调控细胞
Dennis Wolf1,2,3, Teresa Gerhardt1,2,4, Holger Winkels1
1Laboratory of Inflammation Biology(D.W., T.G., H.W., A.B.P., Y.G., K.B., J.M., L.B., K.K., M.V., E.E., A.A., M.S., T.K., K.L.), La Jolla Institute for Immunology, CA.
Circulation
|July 25, 2020
概括
动脉样硬化涉及自动反应的CD4+T细胞. 最初对Apolipoprotein B (apoB) 的保护性T细胞 (Tregs) 可能会变得致病,无法预防疾病的进展.
科学领域:
- 免疫学
- 心血管研究
- 自体免疫性
背景情况:
- 动脉样硬化包括CD4+T辅助细胞和Apolipoprotein B (apoB) 作为自身抗原.
- 虽然已知有致病性T助手1型 (TH1) 细胞,但在健康个体中建议使用特定于apoB的动脉保护性调节性T细胞 (Tregs).
研究的目的:
- 在动脉样硬化中研究apoB反应性T细胞的功能.
- 了解ApoB-反应性Tregs与致病性TH1细胞之间的关系.
主要方法:
- 使用MHCII类四分体来追踪对小鼠ApoB978-993反应的单个T细胞.
- 使用单细胞RNA测序和流细胞测量来分析T细胞转录组和表型.
- 在超脂症小鼠中进行了采用转移实验.
主要成果:
- 在健康小鼠中,ApoB反应性T细胞显示Treg-like转录组,但FoxP3表达低.
- 单细胞测序揭示了apoB+ T细胞中的混合TH签名 (TH1,TH2,TH17,Tfh).
- 在动脉样硬化中,ApoB+ T细胞增加,转化为致病性TH1/TH17表型,并丧失Treg标志物.
- 采用apoB+Tregs的转移并没有防止动脉样硬化.
结论:
- 在动脉样硬化中,ApoB反应性T细胞表现出意想不到的混合表型.
- 对apoB的自身免疫反应最初可能是保护性的,但在疾病中变得失调.
- ApoB自反应Tregs是动脉样硬化治疗的潜在细胞标.
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