ILC2 regulate a Pi16+ fibroblast progenitor niche in the pancreas (acute pancreatitis scRNA-seq)

Local fibroblast development and densities underpin their role in regulating organ function and inflammation, although it remains unclear how tissue fibroblast topography is controlled in situ. Here we define group 2 innate lymphoid cells (ILC2) as key regulators of fibroblast homeostasis in the pancreas. We show that ILC2 co-localise with Pi16+Dpp4+Ly6c+Il33+ fibroblast progenitors in an interstitial niche of the exocrine pancreas, which demarcates and encapsulates the organ parenchyma. ILC2 specifically regulate the expansion of this progenitor population, while paradoxically also restraining differentiated intra-parenchymal Col15a1+ fibroblasts under inflammatory conditions. These homeostatic circuits reinforce fibroblast numbers after injury and set an inflammatory threshold at steady-state. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.