衰老改变子宫内膜树突细胞功能和人类生殖器粘膜中的非传统的双阴性T细胞
Siddharth Parthasarathy1, Zheng Shen2, Francisco J Carrillo-Salinas1
1Department of Immunology, Tufts University School of Medicine, Boston, MA, USA.
Immunity & ageing : I & A
|July 14, 2023
概括
女性生殖道中的双阴性T细胞随着年龄的增长而发生变化,影响生殖健康和感染易感性. 了解DN T细胞的这些与年龄相关的变化,为改善妇女健康提供了新的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 生殖生物学 生殖生物学
- 老年学是一门学科.
背景情况:
- 生殖器免疫功能平衡生殖和病原体防御.
- 老龄化增加了生殖器感染和妇科癌症的风险.
- 女性生殖道中细胞介导免疫的机制和衰老的影响尚不清楚.
- 非传统的双阴性 (DN) T 细胞 (TCRαβ+,CD4-,CD8-) 参与了小鼠的繁殖,但在人类中没有特征.
研究的目的:
- 研究衰老对人类女性生殖道中DN T细胞的诱导,分布和功能的影响.
- 描述DN T细胞作为生殖器组织中的一个独特的子集.
- 探索DN T细胞功能的与年龄相关的变化及其影响.
主要方法:
- 对27至77岁妇女的生殖器组织进行分析.
- 流细胞测量以评估T细胞群和标记物.
- 单细胞RNA测序和基标记抗体测序用于表型和转录概况.
- 使用生殖器树突细胞 (DCs) 的TFGβ依赖诱导试验.
主要成果:
- 生殖器DCs,特别是CD1a+DCs,通过TFGβ诱导DN T细胞的增殖.
- 在老年妇女中,DN T细胞诱导和DCs的细胞因子产生增强.
- DN T 细胞形成了一个独特的子集,具有独特的恒常性,调节性,细胞毒性和抗病毒功能.
- DN T 细胞表现出抑制检查点和与生俱来的抗病毒途径的增强表达.
- 观察到基因DN T细胞的年龄依赖和位点依赖的再分配和功能变化.
- 在子宫内膜DN T细胞中增加了细胞毒性潜力,但随着年龄的增长在子宫外中减少.
结论:
- 在女性生殖道中深入描述DN T细胞诱导和功能.
- 为改善老年妇女生殖结果提供了新的机制性见解.
- 提供了潜在的策略,以提高对感染和妇科癌症的保护与年龄.
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