人类呼吸上皮细胞的过敏炎症记忆
Jose Ordovas-Montanes1,2,3,4,5,6, Daniel F Dwyer7,8, Sarah K Nyquist1,2,3,4,5,9,10
1Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature
|August 24, 2018
概括
慢性鼻炎涉及由于基底干细胞的改变而减少的上皮多样性. 这些细胞保留过敏记忆,导致持续的呼吸道炎症和屏障功能障碍.
科学领域:
- 免疫学
- 细胞生物学
- 呼吸系统医学
背景情况:
- 障碍组织功能障碍是慢性炎症疾病的核心原因.
- 上呼吸道的保护依赖于从基底干细胞区分出来的特殊上皮细胞.
- 过敏性炎症,特别是2型免疫,导致慢性鼻炎,从鼻炎到鼻,基底细胞增生作为严重疾病标志物.
研究的目的:
- 研究基底细胞在慢性鼻炎和屏障组织功能障碍中的作用.
- 对人类慢性鼻炎的细胞类型和子集进行分析,重点关注2型炎症.
- 识别基底的多胞体形成和持久性的分子机制.
主要方法:
- 从人体手术慢性鼻炎样本 (n=12) 的 18,036 个细胞的大规模并行单细胞RNA测序 (Seq-Well).
- 使用 18,704 个来自鼻的细胞进行比较分析 (n=9),以确定健康,炎症和多细胞的特征.
- 活体培养基细胞的功能测试和IL-4受体α子单元阻塞的体内测试.
主要成果:
- 非多体和多体组织间的上皮区分显著差异,显示多体的细胞多样性减少.
- 聚体表现为基底细胞增生,腺细胞减少,分泌细胞抗菌表达改变.
- 与细胞内在,表观遗传和外在因素相关的基底原体差异化轨迹;基底细胞保留IL-4/IL-13暴露记忆.
结论:
- 由于基底细胞的功能转移导致的上皮多样性减少,这标志着2型免疫介导屏障组织功能障碍.
- 皮质干细胞可能通过存储过敏记忆来延续慢性鼻炎.
- 针对IL-4受体通路提供了改变呼吸道上皮细胞状态的潜在治疗策略.
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