Tissue-regulatory T cells influence anti-cancer and pro-repair functions in the exocrine pancreas
Regulatory T cells are fundamentally important for maintaining immune homeostasis, and their potent immune-suppressive roles make them attractive immunotherapeutic targets in cancer. Recent work suggests potential functions of tissue-resident Tregs (trTregs) in tissue-repair and epithelial cell homeostasis. Here, we describe a rare population of trTreg in the exocrine pancreas. We show that these cells share common features of trTregs, including expression of the IL-33 receptor ST2 and production of the epithelial growth factor Amphiregulin, and display an oligoclonal T cell receptor repertoire. Using a mouse model of acute pancreatitis, we show that pancreatic Tregs rapidly expand upon release of IL-33 by fibroblasts. Moreover, depletion of Tregs after initiation of pancreatic injury impairs the regeneration of the exocrine parenchyma. This effect is due, in part, through a direct effect of Tregs on acinar cell proliferation. Finally, we show that transient Treg depletion in established orthotopic pancreatic tumours leads to tumour rejection yet provokes long-lasting damages to surrounding exocrine parenchyma. In all, our results demonstrate the tissue-repair capacity of pancreatic Tregs, and highlight a dualistic role of these cells in the pancreatic tumour ecosystem, with their harmful immune-suppressive function in the tumour coupled to a beneficial tissue-repair function in the surrounding tissue.
Authors
- Sheng Lee
- Silvain Pinaud (ORCID: https://orcid.org/0000-0002-9541-3611)
- Tsz Y. So
- Céline Garcia (ORCID: https://orcid.org/0000-0002-8319-6613)
- Andrew N.j. Mckenzie
- Charlotte Simpson (ORCID: https://orcid.org/0000-0002-8410-7870)
- Shwetha Raghunathan
- James E. D. Thaventhiran (ORCID: https://orcid.org/0000-0001-8616-074X)
- Timotheus Y.F. Halim (ORCID: https://orcid.org/0000-0001-9773-0023)
- Kourosh Saeb‐Parsy (ORCID: https://orcid.org/0000-0002-0633-3696)
- Orian Bricard (ORCID: https://orcid.org/0000-0003-3976-7228)
- Gianmarco Raddi (ORCID: https://orcid.org/0000-0003-1056-5403)
- Weike Luo (ORCID: https://orcid.org/0009-0008-1337-6484)
- Giulia Biffi (ORCID: https://orcid.org/0000-0003-4592-0970)
- Martijn J. Schuijs (ORCID: https://orcid.org/0000-0001-6433-6417)
- Adrian Liston (ORCID: https://orcid.org/0000-0002-6272-4085)
- Julie Stockis (ORCID: https://orcid.org/0000-0003-4911-6891)
- Panagiotis Papadopoulos (ORCID: https://orcid.org/0000-0002-1928-6534)
- Stela Monk (ORCID: https://orcid.org/0009-0002-5634-7233)
- Camille Amourette
- Menna R. Clatworthy
- Rebecca Brais
- Eva Serrao
- Duncan I. Jodrell
- Joaquín Araos Henríques
- Thomas Yip
- Siong-Seng Liau
- Ashley Sawle
- Stephanie Mack
- Shaun Png
Institutions
- Babraham Institute (GB)
- MRC Laboratory of Molecular Biology (GB)
- University of Cambridge (GB)
- Cancer Research UK (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- de Duve Institute (BE)
- MRC Toxicology Unit (GB)
- NIHR Cambridge Biomedical Research Centre (GB)
- Medical Research Council (GB)
- UCLouvain (BE)
Publication Details
- Journal
- Gut
- Published
- 2026-11-04
- DOI
- https://doi.org/10.1136/gutjnl-2025-337515
- Citations
- 1
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 2.29
Funders
- Wellcome Trust
- Cancer Research UK