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

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

  • Sci Adv. 2025 Aug 22;11(34):eadt9645. doi: 10.1126/sciadv.adt9645.
Yuwei Xu 1,  Zhen Xiong 1,  Peikang Zhang 1 2,  Runyuan Wu 1 2,  Cunzhen Li 1 2,  Hui Guo 1,  Ying Du 1,  Xiaoxiao Zhu 1,  Dongdong Fan 1,  Hongzhe Fan 1,  Yong Tian 1 2,  Yun Chen 3,  Zusen Fan 1 2 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 2 University of Chinese Academy of Sciences, Beijing, China.
  • 3 The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Wuxi; Department of Immunology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
  • 4 Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, China.
PMID: 40845099 DOI: 10.1126/sciadv.adt9645
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 CA2+ and RhoA signaling pathways. TDCA-P2Y10 engagement induces Zfp414 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.

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