Science (New York, N.Y.) · 2026
ILC2s regulate a fibroblast progenitor niche in the pancreas.
СтатьяНазвание и аннотация: Перевод в очереди
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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, Jørgensen Claus, McKenzie Andrew N J, Acton Sophie E, Seale Patrick, Clatworthy Menna R, Buechler Matthew B, Halim Timotheus Y F
Аннотация
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.