ILC2s regulate a fibroblast progenitor niche in the pancreas
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 (ILC2) as key regulators of fibroblast homeostasis in the pancreas. ILC2 co-localised with fibroblasts expressing the genes Pi16(+)Dpp4(+)Ly6c(+) in an interstitial niche of the exocrine pancreas, which encapsulates the organ parenchyma. ILC2 specifically regulated the expansion of Pi16(+)Dpp4(+)Ly6c(+) fibroblasts, which have progenitor capacity, while restraining differentiated intra-parenchymal 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 tumours 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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BibTeX
@article{yip2026ilc2s,
title = {{ILC2s regulate a fibroblast progenitor niche in the pancreas}},
author = {Thomas Yip and Julie Stockis and Charlotte Simpson and Erika Mccartney and Shwetha Raghunathan and Martha Rangel-Sosa and Sydney Hummel and Julia Moreno-Vicente and Gianmarco Raddi and Celine Garcia and Rugile Linkute and Silvain Pinaud and Maye Cheng and Lesley Hill and T. Michael Underhill and Hans-Reimer Rodewald and Christoph Schneider and Claus Jørgensen and Andrew N.J. Mckenzie and Sophie Acton and Patrick Seale and Menna Clatworthy and Matthew Buechler and Timotheus Halim},
journal = {Science},
year = {2026},
month = jul,
doi = {10.1126/science.aea5113},
url = {https://hal.science/hal-05793511v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - ILC2s regulate a fibroblast progenitor niche in the pancreas
AU - Thomas Yip
AU - Julie Stockis
AU - Charlotte Simpson
AU - Erika Mccartney
AU - Shwetha Raghunathan
AU - Martha Rangel-Sosa
AU - Sydney Hummel
AU - Julia Moreno-Vicente
AU - Gianmarco Raddi
AU - Celine Garcia
AU - Rugile Linkute
AU - Silvain Pinaud
AU - Maye Cheng
AU - Lesley Hill
AU - T. Michael Underhill
AU - Hans-Reimer Rodewald
AU - Christoph Schneider
AU - Claus Jørgensen
AU - Andrew N.J. Mckenzie
AU - Sophie Acton
AU - Patrick Seale
AU - Menna Clatworthy
AU - Matthew Buechler
AU - Timotheus Halim
PY - 2026
DA - 2026/07/02
JO - Science
DO - 10.1126/science.aea5113
UR - https://hal.science/hal-05793511v1
AB - 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 (ILC2) as key regulators of fibroblast homeostasis in the pancreas. ILC2 co-localised with fibroblasts expressing the genes Pi16(+)Dpp4(+)Ly6c(+) in an interstitial niche of the exocrine pancreas, which encapsulates the organ parenchyma. ILC2 specifically regulated the expansion of Pi16(+)Dpp4(+)Ly6c(+) fibroblasts, which have progenitor capacity, while restraining differentiated intra-parenchymal 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 tumours and controlled cancer associated fibroblast ontogeny and density. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.
SN - 0036-8075
SN - 1095-9203
ER -