Fibroblasts restrain gut inflammation by IGF1-dependent regulation of innate lymphocytes
Fibroblasts exhibit phenotypic and functional heterogeneity in chronic inflammatory diseases, but how these changes impact immune outcomes remains poorly understood. We identified that a fibroblast population expressing insulin-like growth factor 1 (IGF1) was reduced in patients with inflammatory bowel disease (IBD). Using mouse models of intestinal inflammation, we found cross-talk between IGF1-expressing fibroblasts and group 3 innate lymphoid cells (ILC3s). IGF1 stimulation limited the abilit
Fibroblasts exhibit phenotypic and functional heterogeneity in chronic inflammatory diseases, but how these changes impact immune outcomes remains poorly understood. We identified that a fibroblast population expressing insulin-like growth factor 1 (IGF1) was reduced in patients with inflammatory bowel disease (IBD). Using mouse models of intestinal inflammation, we found cross-talk between IGF1-expressing fibroblasts and group 3 innate lymphoid cells (ILC3s). IGF1 stimulation limited the ability of ILC3s to produce C-X-C motif chemokine ligand 10 (CXCL10) and recruit plasmacytoid dendritic cells (pDCs) to restrain gut inflammation. We propose that this regulatory pathway is conserved in human ILC3s but may become impaired in IBD. Our results define that anti-inflammatory fibroblasts safeguard the gut through regulation of an innate lymphocyte–pDC axis.
