微生物群代谢产物牛磺脱氧胆酸通过与P2Y10受体结合维持固有淋巴细胞在肠道组织中的驻留。

Microbiota metabolite taurodeoxycholic acid maintains intestinal tissue residency of innate lymphoid cells via engagement with P2Y10 receptor.

作者信息

Xu Yuwei, Xiong Zhen, Zhang Peikang, Wu Runyuan, Li Cunzhen, Guo Hui, Du Ying, Zhu Xiaoxiao, Fan Dongdong, Fan Hongzhe, Tian Yong, Chen Yun, Fan Zusen

机构信息

State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

University of Chinese Academy of Sciences, Beijing, China.

出版信息

Sci Adv. 2025 Aug 22;11(34):eadt9645. doi: 10.1126/sciadv.adt9645.

DOI:10.1126/sciadv.adt9645

PMID:40845099

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12372891/

Abstract

Innate lymphoid cells (ILCs) play critical roles in innate immunity, epithelial barrier protection, and tissue homeostasis. However, the maintenance machinery of intestinal tissue residency of ILCs remains elusive. Here, we show that gut microbiota is necessary for the maintenance of intestinal tissue residency of ILCs. Microbiota metabolite taurodeoxycholic acid (TDCA) binds to P2Y10 receptor on ILCs to initiate downstream Ca and RhoA signaling pathways. TDCA-P2Y10 engagement induces transcription to prime expression of CD69 and integrin αE on ILCs, leading to intestinal residency of ILCs. Moreover, decreased levels of TDCA or P2Y10 deficiency abrogates the intestinal residency of ILCs, resulting in severer intestinal inflammation. Of note, TDCA administration can enhance intestinal tissue residency of ILCs and promote protection against intestinal inflammation. Thus, TDCA might be used as a potential drug to treat patients with inflammatory bowel disease.

摘要

固有淋巴细胞（ILCs）在固有免疫、上皮屏障保护和组织稳态中发挥着关键作用。然而，ILCs在肠道组织中定居的维持机制仍不清楚。在这里，我们表明肠道微生物群对于ILCs在肠道组织中的定居维持是必要的。微生物群代谢产物牛磺脱氧胆酸（TDCA）与ILCs上的P2Y10受体结合，启动下游的钙和RhoA信号通路。TDCA与P2Y10的相互作用诱导转录，启动ILCs上CD69和整合素αE的表达，导致ILCs在肠道定居。此外，TDCA水平降低或P2Y10缺乏会消除ILCs在肠道的定居，导致更严重的肠道炎症。值得注意的是，给予TDCA可以增强ILCs在肠道组织中的定居，并促进对肠道炎症的保护。因此，TDCA可能用作治疗炎症性肠病患者的潜在药物。