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Persistent Inflammation of the Rectum in Perianal-Fisulizing Crohn's Disease Associates with Goblet Cell Function

ABSTRACT: Persistent Inflammation of the Rectum in Perianal-Fisulizing Crohn's Disease Associates with Goblet Cell Function

PROVIDER: PRJNA934333 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23446035_1.fastq.gz	Fastqsanger.gz
	SRR23446035_2.fastq.gz	Fastqsanger.gz
	SRR23446036_1.fastq.gz	Fastqsanger.gz
	SRR23446036_2.fastq.gz	Fastqsanger.gz
	SRR23446037_1.fastq.gz	Fastqsanger.gz

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Persistent Inflammation of the Rectum in Perianal-Fisulizing Crohn's Disease Associates with Goblet Cell Function

Project description:Perianal Fistulizing Crohn’s Disease (perianal-CD) is a debilitating form of CD typically associated with prolonged periods of morbidity. Leveraging single-cell RNA sequencing, rectal mucosal tissue was sequenced from individuals following anti-TNF biologic therapy having either active perianal-CD and inflamed rectal mucosa or healed perianal-CD but non-inflamed mucosa. Single cell transcriptomic profiles of the inflamed and non-inflamed tissue were contrasted to test for specific cellular subsets of rectal epithelial and immune cell compartments associated with inflamed perianal disease. We identified eight broad classes of epithelial, six of immune, and a small population of stromal cells in the rectal mucosa. There was an increase in colonocytes in the non-inflamed tissue compared to the inflamed tissue, and an increase of naïve b cells and plasma cells associated with inflamed tissue. The cell type proportions of immune cells, highlighted patient heterogeneity of cell type abundance and potential dysregulation of both the immune and epithelial compartment. We also note enrichment of IgG plasma cells in inflamed tissue of two donors and expansion of IgA plasma cells of non-inflamed tissue in two donors. Differential gene expression analysis of goblet cells revealed enrichment of inflammatory pathways, such as IL6 and interferon gamma signaling, in inflamed tissue. These inflammatory pathways might affect tight junctions between epithelial cells leading to increased permeability and potentially affect fistula formation. Our findings suggest dysregulation of crypt maturation during persistent inflammation and over-abundance of goblet cells and colonocyte precursors in inflamed tissue of perianal-CD.

2023-02-20 | GSE225199 | GEO

TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients [RNA-seq]

Project description:Perianal fistulizing disease (PFD) is one of the complications observed in Crohn's Disease patients, which consist of the formation of new tracks connecting the anal canal or the rectum with the perianal region. Applying scRNA-seq analysis in the rectum of patients with and without PFD revealed alterations in the stromal compartment as a response to cytokines such as TNF, TGFb and LTB. To investigate the downstream signature of these cytokines especifically in intestinal fibroblasts, we sequenced human intestinal primary fibroblasts upon stimulation to TNF, TGFb and LTB.

2026-01-20 | GSE291014 | GEO

TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients.

Project description:TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients.

| PRJNA1272051 | ENA

TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients.

Project description:TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients.

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Persistent Inflammation of the Rectum in Perianal Fistulizing Crohn's Disease Is Associated With Goblet Cell Function.

Project description: Not available

| S-EPMC11307797 | biostudies-literature

TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients.

Project description:Perianal fistulizing disease (PFD) is a complication that affects about 20% of Crohn’s disease (CD) patients and whose etiology remains unknown. To identify predisposing events driving fistula formation, we investigated cell-specific alterations in the rectal mucosa of CD patients with PFD. Rectal biopsies from CD patients with or without PFD (CD+PFD and CD, respectively; n=31) were subjected to single-cell RNA sequencing. Functional analyses were conducted using peripheral CD3+ T cells, intestinal tissue explants, primary fibroblasts and 2D-epithelial monolayer cell cultures. The rectal mucosa of CD+PFD patients is imprinted with cellular and transcriptomic alterations specific to PFD and independent of luminal inflammation, potentially driven by TL1A activation in CD4+ T cells. We identified lymphotoxin beta (LTB or its functional heterotrimer LTα1β2) as a novel mediator downstream of TL1A that, along with IL-22, induces a PFD-associated signature in rectal fibroblast and epithelial cells, respectively. This signature includes an increased abundance of fibroblasts, an induction of matrix-degrading enzymes and transcriptomic rewiring of the lamina propria S1 fibroblasts, as well as an anti-bacterial and immune responses in epithelial cells. Notably, the induction of LTα1β2 and IL-22 occurs independently of TNF signaling, revealing a new TL1A-LTα1β2/IL-22 axis that remains active under anti-TNF therapy. Our findings revealed unique cellular alterations in the rectum of CD patients with PFD, highlighting the previously unrecognized involvement of TL1A in mediating this signature and supporting the need for exploring the role of TL1A inhibition as a therapeutic approach for PFD.

2026-01-20 | GSE298981 | GEO

TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients [scRNA-seq]

Project description:TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients [scRNA-seq]

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TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients [RNA-seq]

Project description:TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients [RNA-seq]

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Effects of psychological stress on gene expression in the mouse rectum.

2009-02-14 | GSE11910 | GEO

Transcription profiling of mouse rectum after physiological stress

Project description:Using isolation stress model, we showed that goblet cell-dependent mucosal barrier functions in the mouse rectum was more vulnerable to stress than the colon. We also found that isolation stress specifically stimulated IL-18 production only in the rectum. Furthermore, the crucial role of IL-18 in the stress response of the mouse rectum was confirmed using IL-18 knockout mice. Microarray analysis was used to assess the stress response and to identify responsible genes for the vulnerability of the mouse rectum to isolation stress. Experiment Overall Design: Total RNA was prepared from the colon and the rectum of wild-type and IL-18 knockout mice before isolation and 8 days after starting isolation. The one GSM sample of microarray analysis was made by pooling an equal amount of total RNA 5 mice of each group. Agilent whole mouse genome oligonucleotide microarray was used to measure gene expression in these samples according to the manufactureâ??s protocol.

2009-02-26 | E-GEOD-11910 | biostudies-arrayexpress

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