ILC2s regulate a fibroblast progenitor niche in the pancreas

Yip, Thomas;Stockis, Julie;Simpson, Charlotte;Mccartney, Erika;Acton, Sophie;et.al.
(2026) Science — Vol. 393, n° 6806, p. 58-75 (2026)

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Authors
  • Yip, Thomasorcid-logoUniversity of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
    Author
  • Stockis, JulieUCLouvain
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  • Simpson, Charlotteorcid-logoUniversity of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
    Author
  • Mccartney, Erikaorcid-logoUniversity of Toronto, Department of Immunology, Toronto, ON, Canada.
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  • Acton, Sophieorcid-logoLaboratory for Molecular Cell Biology, University College London, London, UK.
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  • et. al.
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Abstract
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.
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Yip, T., Stockis, J., Simpson, C., Mccartney, E., Raghunathan, S., Rangel-Sosa, M., Hummel, S., Moreno-Vicente, J., Raddi, G., Garcia, C., Linkute, R., Pinaud, S., Cheng, M., Hill, L., Underhill, T., Rodewald, H.-R., Schneider, C., Jørgensen, C., Mckenzie, A., et al. (2026). ILC2s regulate a fibroblast progenitor niche in the pancreas. Science, 393(6806), 58-75. https://doi.org/10.1126/science.aea5113 (Original work published 2026)