皮肤内生淋巴细胞汇聚到致病效应状态
Piotr Bielecki1,2, Samantha J Riesenfeld3,4,5, Jan-Christian Hütter6
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. piotr.stanislaw.bielecki@gmail.com.
Nature
|February 4, 2021
概括
皮肤先天性淋巴细胞 (ILCs) 可以在牛皮期间由IL-23信号驱动过渡到致病性ILC3类状态. 组织内存在的ILC对这种炎症至关重要,突出显示免疫细胞的动态可塑性.
科学领域:
- 免疫学
- 细胞生物学
- 皮肤病学
背景情况:
- 组织内固有的淋巴细胞 (ILC) 是阻碍免疫和局部反应的关键参与者.
- 根据转录因子和细胞因子概况,ILCs被分为亚型 (ILC1,ILC2,ILC3).
- 在牛皮中,由IL-23驱动的IL- 17和IL- 22与IL- 3相关的细胞因子会导致皮肤炎症.
研究的目的:
- 调查皮炎是否是由预先发生的ILC或通过细胞状态过渡引起的.
- 在诱导牛皮时描述皮肤ILC的动态转录格局.
主要方法:
- 使用IL-23或伊米基莫德诱导小鼠的牛皮.
- 在一段时间内对皮肤ILC进行单细胞RNA测序 (scRNA-seq).
- 在体外实验,单细胞ATAC测序 (scATAC-seq) 和体内命运映射.
主要成果:
- 牛皮炎重新配置皮肤ILCs的谱,汇聚到一种致病性ILC3类状态.
- 组织内存在的ILC,而不是循环ILC,足以驱动病理.
- scRNA-seq显示了流体ILC状态的转录连续性,在疾病诱导时转向ILC3类表型.
- 已证实静态和ILC2ILC状态具有过渡潜力.
结论:
- 皮肤ILC表现出显著的可塑性,因炎症触发而在状态之间转换.
- 免疫细胞在健康组织中的动态适应会导致病态重塑,
- 了解这些细胞状态转变对于开发针对性治疗诸如牛皮等炎症性皮肤疾病至关重要.
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