ILC2s regulate a fibroblast progenitor niche in the pancreas

• 成果类型: Article
• 署名作者: Yip, Thomas; Stockis, Julie; Simpson, Charlotte; McCartney, Erika E.; Raghunathan, Shwetha; Rangel-Sosa, Martha M.; Hummel, Sydney N.; Moreno-Vicente, Julia; Raddi, Gianmarco; Garcia, Celine; Linkute, Rugile; Pinaud, Silvain; Cheng, Maye F.; Hill, Lesley A.; Underhill, T. Michael; Rodewald, Hans-Reimer; Schneider, Christoph; Jorgensen, Claus; McKenzie, Andrew N. J.; Acton, Sophie E.; Seale, Patrick; Clatworthy, Menna R.; Buechler, Matthew B.; Halim, Timotheus Y. F.
• 署名单位: CRUK Cambridge Institute; University of Cambridge; University of Toronto; University of British Columbia; Helmholtz Association; German Cancer Research Center (DKFZ); University of Zurich; University of Manchester; Cancer Research UK; MRC Laboratory Molecular Biology; University of London; University College London; University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Pennsylvania Medicine; University of Cambridge; University of Toronto; University Health Network Toronto
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aea5113
• 发表日期: 2026-07-02
• 页码: eaea5113
• 关键词: innate lymphoid-cells; t-cells; immunity; eosinophils; homeostasis; distinct; death; il-33

摘要

Local fibroblast development and densities influence organ health and disease, although it remains unclear how tissue fibroblast topography is controlled in situ. Here, we defined Group 2 innate lymphoid cells (ILC2s) as key regulators of fibroblast homeostasis in the pancreas. ILC2s colocalized with fibroblasts expressing the genes Pi16+Dpp4+Ly6c+ in an interstitial niche of the exocrine pancreas, which encapsulates the organ parenchyma. ILC2s specifically regulated the expansion of Pi16+Dpp4+Ly6c+ fibroblasts, which have progenitor capacity, while restraining differentiated intraparenchymal Col15a1+ fibroblasts during inflammation. These circuits reinforced fibroblast numbers after injury and set an inflammatory threshold. The ILC2 and Pi16+Dpp4+Ly6c+ fibroblast progenitor niche expanded around tumors and controlled cancer-associated fibroblast ontogeny and density. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.