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 (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.
Article Details
Journal Info
Science
American Association for the Advancement of Science
Authors (24)
Thomas Yip
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Julie Stockis
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Charlotte Simpson
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Erika E. McCartney
University of Toronto, Department of Immunology, Toronto, ON, Canada.
Shwetha Raghunathan
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Martha M. Rangel-Sosa
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Sydney N. Hummel
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Julia Moreno-Vicente
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Gianmarco Raddi
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Celine Garcia
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Rugile Linkute
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Silvain Pinaud
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Maye F. Cheng
University of Toronto, Department of Immunology, Toronto, ON, Canada.
Lesley A. Hill
Department of Cellular and Physiological Sciences and Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
T. Michael Underhill
Department of Cellular and Physiological Sciences and Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
Hans-Reimer Rodewald
Division of Cellular Immunology, German Cancer Research Center; Heidelberg, Germany.
Christoph Schneider
Department of Physiology, University of Zurich, Zurich, Switzerland.
Claus Jørgensen
University of Manchester, Cancer Research UK Manchester Institute, Manchester, UK.
Andrew N.J. McKenzie
MRC Laboratory of Molecular Biology, Cambridge, UK.
Sophie E. Acton
Laboratory for Molecular Cell Biology, University College London, London, UK.
Patrick Seale
Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Menna R. Clatworthy
Matthew B. Buechler
University of Toronto, Department of Immunology, Toronto, ON, Canada.
Timotheus Y. F. Halim
University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.