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Epithelial EP4 plays an essential role in maintaining homeostasis in colon

ABSTRACT: Epithelial EP4 plays an essential role in maintaining homeostasis in colon

PROVIDER: PRJNA560350 | ENA |

REPOSITORIES: ENA

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Epithelial EP4 plays an essential role in maintaining homeostasis in colon

Project description:The EP4 receptor is known to mediate the protective effect of prostaglandin (PG) E2 in the gastrointestinal tract; however, the exact role of epithelial EP4 in intestinal pathophysiology remains unknown. We investigated the role of epithelial EP4 in maintaining colonic homeostasis by characterizing the intestinal epithelial cell-specific EP4 knockout (EP4 cKO) mice. We found a significant enrichment of genes involved in apoptosis-related pathways in the EP4 cKO colons. Moreover, inflammation-associated pathways were highly enriched and revealed more than half of the top 20 pathways related to immune response.

2019-10-29 | GSE135859 | GEO

Epithelial EP4 plays an essential role in maintaining homeostasis in colon.

Project description:Colonic epithelial cells comprise the mucosal barrier, and their dysfunction promotes microbial invasion from the gut lumen and induces the development of intestinal inflammation. The EP4 receptor is known to mediate the protective effect of prostaglandin (PG) E2 in the gastrointestinal tract; however, the exact role of epithelial EP4 in intestinal pathophysiology remains unknown. In the present study, we aimed to investigate the role of epithelial EP4 in maintaining colonic homeostasis by characterizing the intestinal epithelial cell-specific EP4 knockout (EP4 cKO) mice. Mice harboring the epithelial EP4 deletion showed significantly lower colonic crypt depth and lower numbers of secretory cell lineages, as well as impaired epithelial cells in the colon. Interestingly, EP4-deficient colon epithelia showed a higher number of apoptotic cells. Consistent with the defect in mucosal barrier function of colonic epithelia and secretory cell lineages, EP4 cKO colon stroma showed enhanced immune cell infiltration, which was accompanied by increased production of inflammatory cytokines. Furthermore, EP4-deficient colons were susceptible to dextran sulfate sodium (DSS)-induced colitis. Our study is the first to demonstrate that epithelial EP4 loss resulted in potential "inflammatory" status under physiological conditions. These findings provided insights into the crucial role of epithelial PGE2/EP4 axis in maintaining intestinal homeostasis.

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Vascular integrity is essential for maintaining tissue homeostasis

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RIPK1 plays a crucial role in maintaining regulatory T cell homeostasis by inhibiting both RIPK3 and FADD-mediated cell death

Project description:Regulatory T (Treg) cells are a critical for maintaining immune balance in various physiological and pathological conditions. However, the mechanisms underlying Treg homeostasis remain incompletely understood. In this study, we demonstrated that RIPK1 is crucial for Treg cell survival and homeostasis. We generated mice with Treg cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the number of Treg cell caused by excessive cell death. Unlike conventional T cells, Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking the FADD pathway. However, simultaneous removal of both Fadd and Ripk3 completely restored the number of Ripk1-deficient Treg cells by blocking cell death. Our results demonstrated that RIPK1 plays a critical role in regulating Treg cell survival by controlling both necroptosis and apoptosis. These findings provide new insights into the mechanisms of Treg cell homeostasis and suggest potential therapeutic targets for autoimmune diseases.

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Rhodococcus EP4 Aromatic Transcriptomics

Project description:Transcriptomics of Rhodococcus EP4 on ethylphenol, propylguiacol and succiate

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Project description:RIPK1 plays a crucial role in maintaining regulatory T cell homeostasis by inhibiting both RIPK3 and FADD-mediated cell death

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