Fig. 2: An IL-11 cell circuit governs fibrosis.
From: Bidirectional CRISPR screens decode a GLIS3-dependent fibrotic cell circuit
a, Masson’s trichrome-stained Il11f/f and Il11f/f;cre colons (8–18 weeks) treated with water or chronic DSS (left). Total collagen percentage from three pooled experiments (right). Il11f/f-water, n = 10; Il11f/f;cre-water, n = 14; Il11f/f-DSS, n = 17; Il11f/f;cre-DSS, n = 10 mice. b, Colonic hydroxyproline normalized to total protein for tissues from a. c, qPCR quantification of collagens normalized to Eef2 from tissues from a. d, Colon length measurements from a. e, Percentage of IL-11mNG cells across lineages after the indicated treatments. Water-treated, n = 2; DSS-treated, n = 3 mice. f, Masson’s trichrome-stained (left) and immunofluorescence-stained (right) Il11mNG tissues after DSS. Images are representative of three independent experiments. g, Schematic of PDGFRA+ fibroblast isolation from acute and chronic DSS-treated Il11mNG mice (8–14 weeks) (left). Dot plot mapping human fibroblast gene signatures across mouse fibroblasts (right). h, Pseudobulk expression heatmap depicting scaled average expression of Il11 and mNeonGreen from acute and chronic DSS treatment groups. i, Spatial niche-aware probability of intercellular communication. Edge thickness or node size depicts communication strength. Significant signals received by IAFs (left) and sent from activated macrophages (right). j, Immunofluorescence of chronic DSS-treated colons from Il11mNG mice depicting proximal macrophage (CD68, red) and IL-11mNG fibroblast (green) localization. Arrowheads indicate signal adjacency. Images are representative of three independent experiments. k, Spatial projection of IAFs and activated macrophages in non-IBD and CD tissues. l, Dot plot of IAF IL11 expression as a function of proximity to activated macrophages. m, Secreted IL-11 measured from co-cultures of polarized primary human monocyte-derived macrophages, after removal of agonists, with colonic fibroblasts for 24 h. Fibroblasts only, n = 4; fibroblasts + macrophages, n = 2; fibroblasts + polarized macrophages, n = 3 cell lines. Mice were co-housed, and DSS treatment followed the same regimen: acute (2.0%, 7 days), chronic (2.0%, 42 days). Unless otherwise stated, statistics are from two-way analysis of variance (ANOVA) with Tukey’s multiple-comparison test on distinct biological replicates, and error bars indicate s.e.m. NS, not significant. cDC, conventional dendritic cell; IEL, intraepithelial lymphocyte; LP, lamina propria; NK, natural killer; Treg cells, regulatory T cells. Scale bars, 100 μm (a,f), 10 μm (j). Illustrations in g and m created using BioRender. Pokatayev, V. (2025). g, https://BioRender.com/1ildc4h; m, https://BioRender.com/gp42jp3.
