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人源 CD127 阴性 ILC2 具有免疫记忆。

Human CD127 negative ILC2s show immunological memory.

机构信息

Microbiology, Tumor and Cell Biology, Karolinska Institute , Stockholm, Sweden.

Terry Fox Laboratory, British Columbia Cancer , Vancouver, Canada.

出版信息

J Exp Med. 2024 Aug 5;221(8). doi: 10.1084/jem.20231827. Epub 2024 Jun 18.

DOI:10.1084/jem.20231827
PMID:38889332
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11187981/
Abstract

ILC2s are key players in type 2 immunity and contribute to maintaining homeostasis. ILC2s are also implicated in the development of type 2 inflammation-mediated chronic disorders like asthma. While memory ILC2s have been identified in mouse, it is unknown whether human ILC2s can acquire immunological memory. Here, we demonstrate the persistence of CD45RO, a marker previously linked to inflammatory ILC2s, in resting ILC2s that have undergone prior activation. A high proportion of these cells concurrently reduce the expression of the canonical ILC marker CD127 in a tissue-specific manner. Upon isolation and in vitro stimulation of CD127-CD45RO+ ILC2s, we observed an augmented ability to proliferate and produce cytokines. CD127-CD45RO+ ILC2s are found in both healthy and inflamed tissues and display a gene signature of cell activation. Similarly, mouse memory ILC2s show reduced expression of CD127. Our findings suggest that human ILC2s can acquire innate immune memory and warrant a revision of the current strategies to identify human ILC2s.

摘要

ILC2 是 2 型免疫的关键参与者，并有助于维持体内平衡。ILC2 也与哮喘等 2 型炎症介导的慢性疾病的发展有关。虽然已经在小鼠中鉴定出记忆性 ILC2，但尚不清楚人类 ILC2 是否能够获得免疫记忆。在这里，我们证明了 CD45RO（以前与炎症性 ILC2 相关的标志物）在经历过先前激活的静止 ILC2 中持续存在。这些细胞中的很大一部分以组织特异性的方式同时降低经典的 ILC 标志物 CD127 的表达。在分离和体外刺激 CD127-CD45RO+ILC2 后，我们观察到增殖和产生细胞因子的能力增强。CD127-CD45RO+ILC2 存在于健康和炎症组织中，并表现出细胞激活的基因特征。同样，小鼠记忆性 ILC2 表现出 CD127 表达降低。我们的发现表明，人类 ILC2 可以获得先天免疫记忆，这需要对当前鉴定人类 ILC2 的策略进行修订。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/a7165cb54098/JEM_20231827_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/4b4bbdccc393/JEM_20231827_GA.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/dbadf6e30d0d/JEM_20231827_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/11638af3e4d0/JEM_20231827_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/844e14032ba9/JEM_20231827_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/6f779ea3e4a9/JEM_20231827_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/df0ce209c2d3/JEM_20231827_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/3422bd3befe6/JEM_20231827_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/20e5d3e9f188/JEM_20231827_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/45d6f23c4570/JEM_20231827_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/cb3966b5d037/JEM_20231827_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/a8902866a058/JEM_20231827_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/a7165cb54098/JEM_20231827_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/4b4bbdccc393/JEM_20231827_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/ee7b2ddc4a9d/JEM_20231827_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/dbadf6e30d0d/JEM_20231827_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/11638af3e4d0/JEM_20231827_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/844e14032ba9/JEM_20231827_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/6f779ea3e4a9/JEM_20231827_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/df0ce209c2d3/JEM_20231827_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/3422bd3befe6/JEM_20231827_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/20e5d3e9f188/JEM_20231827_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/45d6f23c4570/JEM_20231827_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/cb3966b5d037/JEM_20231827_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/a8902866a058/JEM_20231827_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c06/11187981/a7165cb54098/JEM_20231827_Fig7.jpg

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