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.

Authors:: T Yip, J Stockis, C Simpson, EE McCartney, S Raghunathan, MM Rangel-Sosa, SN Hummel, J Moreno-Vicente, G Raddi, C Garcia, R Linkute, S Pinaud, MF Cheng, LA Hill, TM Underhill, H-R Rodewald, C Schneider, C Jørgensen, ANJ McKenzie, SE Acton, P Seale, MR Clatworthy, MB Buechler, TYF Halim

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