在人体免疫系统成熟期间发生全身免疫活动
Shuai He1, Chun-Ling Luo2, Tao Luo1
1State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R. China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R. China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R. China.
在怀孕期间, 胎儿的免疫细胞是活跃和广泛的, 挑战以前的免疫休眠的信念. 研究人员在胎儿中发现了新的耐受机制和免疫细胞发育途径.
科学领域:
- 免疫学
- 发育生物学
- 基因组学
背景情况:
- 第二个三个月对人类免疫系统的发展至关重要.
- 以前的理解表明胎儿免疫静止,系统活动有限.
- 胎儿外T细胞发育和免疫耐受性的作用需要进一步阐明.
研究的目的:
- 在人类怀孕的第二个三个月全面描述免疫细胞群和它们的发展.
- 研究胎儿环境中的免疫耐受机制.
- 探索胎儿中的造血干细胞 (HSC) 的分布和分化潜力.
主要方法:
- 使用单细胞RNA测序 (scRNA-seq) 和T细胞受体 (TCR) 测序.
- 分析了来自23个胎儿和成人器官的321个样本中的2,868,420个免疫细胞.
- 进行了细胞间通信分析和功能测定.
主要成果:
- 鉴定参与原始T细胞成熟的CD4+T细胞子集.
- 发现了广泛的胎儿记忆/激活的T细胞和器官共享的组织内存克隆,表明了全身免疫活性.
- 发现了两个胎儿免疫耐受机制:ARG1+中性粒细胞和PTGES3/PTGER4信号通路.
- 从各种器官观察出血造干细胞 (HSC) 的分散和分化.
结论:
- 胎儿免疫系统表现出显著的系统性活动和复杂性,与静止模式相反.
- 在胎儿中发现了T细胞发育和免疫耐受性的新途径.
- 造血干细胞在胎儿发育过程中表现出广泛的分布和分化潜力,影响免疫系的多样性.
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