Macrophages in Crohn’s disease creeping fat are predominantly inflammatory and produce calprotectin
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ABSTRACT:
PROVIDER: PRJNA623563 | ENA |
REPOSITORIES: ENA
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Project description:Crohn’s disease is characterized by transmural inflammation and therefore the mesenteric immune compartment has gained interest. However, its significance in Crohn’s disease is largely unclear. Macrophages are plastic cells that adapt their phenotype to environmental stimuli resulting in inflammatory and regulatory macrophage subsets. Hence, their distribution can reflect the overall nature of an immune infiltrate. We show that mesenteric macrophages contain two populations, characterized as CD11b-high and CD11b-dim. The CD11b-dim population is characterized by expression of regulatory markers CD206, CD200R, CD163, PD-L2, CD32. CD11b-high macrophages display an IFNγ induced signature and produce high levels of calprotectin. CD11b-dim and CD11b-high populations were comparable between Crohn’s disease and other indications in expression pattern, but the CD11b-high population was strongly overrepresented in this patient group.
2021-04-07 | GSE148233 | GEO
Project description:A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to cause a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue (MAT) around inflamed and fibrotic bowel, but its role in stricture progression in CD is unclear. In this study, we explore whether CF-derived fibroblasts, the cells primarily responsible for extracellular matrix (ECM) deposition, directly contribute to stricture progression. By performing scRNA-seq and Visium on pediatric CD strictures, we identified a CF-associated, mechanosensitive, CTHRC1+ fibroblast enriched for YAP/TAZ signaling that localized to the fibrotic CF-bowel wall interface within the stricture. We developed a novel mouse model of intestinal fibrosis that exhibited CF and used lineage tracing to show that Postn+ mouse fibroblasts, analogous to human CTHRC1+ fibroblasts, infiltrate fibrotic bowel and deposit ECM in a YAP/TAZ-dependent manner through scRNA-seq. Our findings identify mesenteric fat as a key source of pro-fibrotic fibroblasts that can be therapeutically targeted to limit intestinal fibrosis.
2025-08-23 | GSE275144 | GEO
Project description:A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to cause a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue (MAT) around inflamed and fibrotic bowel, but its role in stricture progression in CD is unclear. In this study, we explore whether CF-derived fibroblasts, the cells primarily responsible for extracellular matrix (ECM) deposition, directly contribute to stricture progression. By performing scRNA-seq, Visium and Xenium on pediatric CD strictures, we identified a CF-associated, mechanosensitive, CTHRC1+ fibroblast enriched for YAP/TAZ signaling that localized to the fibrotic CF-bowel wall interface within the stricture. We developed a novel mouse model of intestinal fibrosis that exhibited CF and used lineage tracing to show that Postn+ mouse fibroblasts, analogous to human CTHRC1+ fibroblasts, infiltrate fibrotic bowel and deposit ECM in a YAP/TAZ-dependent manner through scRNA-seq. Our findings identify mesenteric fat as a key source of pro-fibrotic fibroblasts that can be therapeutically targeted to limit intestinal fibrosis.
2025-09-17 | GSE296331 | GEO
Project description:A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to cause a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue (MAT) around inflamed and fibrotic bowel, but its role in stricture progression in CD is unclear. In this study, we explore whether CF-derived fibroblasts, the cells primarily responsible for extracellular matrix (ECM) deposition, directly contribute to stricture progression. By performing scRNA-seq and Visium on pediatric CD strictures, we identified a CF-associated, mechanosensitive, CTHRC1+ fibroblast enriched for YAP/TAZ signaling that localized to the fibrotic CF-bowel wall interface within the stricture. We developed a novel mouse model of intestinal fibrosis that exhibited CF and used lineage tracing to show that Postn+ mouse fibroblasts, analogous to human CTHRC1+ fibroblasts, infiltrate fibrotic bowel and deposit ECM in a YAP/TAZ-dependent manner through scRNA-seq. Our findings identify mesenteric fat as a key source of pro-fibrotic fibroblasts that can be therapeutically targeted to limit intestinal fibrosis.
2025-08-23 | GSE275145 | GEO
Project description:A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to cause a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue (MAT) around inflamed and fibrotic bowel, but its role in stricture progression in CD is unclear. In this study, we explore whether CF-derived fibroblasts, the cells primarily responsible for extracellular matrix (ECM) deposition, directly contribute to stricture progression. By performing scRNA-seq and Visium on pediatric CD strictures, we identified a CF-associated, mechanosensitive, CTHRC1+ fibroblast enriched for YAP/TAZ signaling that localized to the fibrotic CF-bowel wall interface within the stricture. We developed a novel mouse model of intestinal fibrosis that exhibited CF and used lineage tracing to show that Postn+ mouse fibroblasts, analogous to human CTHRC1+ fibroblasts, infiltrate fibrotic bowel and deposit ECM in a YAP/TAZ-dependent manner through scRNA-seq. Our findings identify mesenteric fat as a key source of pro-fibrotic fibroblasts that can be therapeutically targeted to limit intestinal fibrosis.
2025-08-23 | GSE275148 | GEO
Project description:Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Visium]
| PRJNA1149687 | ENA
Project description:The goal of this study is to correlate the transcriptional response of S. aureus cells grown in Calprotectin treated medium with that of cells grown in Mn or Zn depletion conditions. Keywords: RNA sample Staphylcoccus aureus strain Newman was grown to mid-log phase in Calprotectin treated medium or medium lacking either Zn or Mn. RNA was isolated, labeled and hybridized to an S. aureus Affymetrix GeneChip. Biological replicates are indicated as A, B, or C.
2010-05-26 | E-GEOD-9828 | biostudies-arrayexpress
Project description:Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Human scRNA-seq]
| PRJNA1149688 | ENA
Project description:Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Mouse scRNA-seq]
| PRJNA1149690 | ENA
Project description:The host protein calprotectin inhibits the growth of a variety of bacterial pathogens through metal sequestration in a process known as 'nutritional immunity'. Staphylococcus aureus growth is inhibited by calprotectin in vitro and calprotectin is localized in vivo to staphylococcal abscesses during infection. However, the staphylococcal adaptations that provide defense against nutritional immunity and the role of metal-responsive regulators are not fully characterized. In this work, we define the transcriptional response of S. aureus and the role of the metal-responsive regulators, Zur, Fur, and MntR, in response to metal limitation by calprotectin exposure. Additionally, we identified genes affecting the fitness of S. aureus during metal limitation through a Transposon sequencing (Tn-seq) approach. Loss of function mutations in clpP, which encodes a proteolytic subunit of the ATP-dependent Clp protease, demonstrate reduced fitness of S. aureus to the presence of calprotectin. ClpP contributes to pathogenesis in vivo in a calprotectin-dependent manner. These studies establish a critical role for ClpP to combat metal limitation by calprotectin and reveal the genes required for S. aureus to outcompete the host for metals.
2024-05-14 | GSE266003 | GEO