ILC2 regulate a fibroblast progenitor niche in the pancreas (Dpp4CreERT2 lineage trace scRNA-seq)

Here we define group 2 innate lymphoid cells (ILC2) as key regulators of fibroblast homeostasis in the pancreas. ILC2 co-localise with Pi16+Dpp4+Ly6c+ fibroblasts in an interstitial niche of the exocrine pancreas, which encapsulates the organ parenchyma.

ILC2 specifically regulate the expansion of Pi16+Dpp4+Ly6c+ fibroblasts, which have progenitor capacity, while paradoxically also restraining differentiated intra-parenchymal Col15a1+ fibroblasts during inflammation. These homeostatic circuits reinforce fibroblast numbers after injury and set an inflammatory threshold. The ILC2-Pi16+Dpp4+Ly6c+ fibroblast progenitor niche expands locally in cancer, and controls cancer associated fibroblast ontogeny and density.