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TCF-1 和 TOX 调控哮喘中肠道 2 类固有淋巴细胞的记忆形成。

TCF-1 and TOX regulate the memory formation of intestinal group 2 innate lymphoid cells in asthma.

机构信息

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Department of Immunology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

出版信息

Nat Commun. 2024 Sep 8;15(1):7850. doi: 10.1038/s41467-024-52252-2.

DOI:10.1038/s41467-024-52252-2
PMID:39245681
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11381517/
Abstract

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45lineageCD90.2NK1.1NKp46ST2KLRG1IL-17RB memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence.

摘要

免疫记忆已扩展到 2 类固有淋巴细胞（ILC2s），但其细胞和分子基础仍不完全清楚。基于屋尘螨（HDM）诱导的小鼠哮喘模型和人类样本，我们应用流式细胞术、联体共生、体内成像和过继性移植来证实 CD45lineageCD90.2NK1.1NKp46ST2KLRG1IL-17RB 记忆样 ILC2s（ml-ILC2s）的持久性、迁移和功能。受 CCR9/CCL25 和 S1P 信号的调节，ml-ILC2s 在哮喘缓解时存在于小肠固有层（siLP）中，随后在再次遇到抗原或警报素时迁移到气道。此外，ml-ILC2s 具有长寿、快速增殖和产生 IL-13 的潜力，并表现出转录特征，Tox 和 Tcf-7 上调。ml-ILC2s 的移植恢复了因 Tox 和 Tcf7 敲低而被取消的哮喘变化。我们的数据确定 siLP ml-ILC2s 为记忆样亚群，可促进哮喘复发。针对 TCF-1 和 TOX 可能是预防哮喘复发的有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd2b/11381517/baccf0714181/41467_2024_52252_Fig7_HTML.jpg
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