Su1193 STING ACTIVATION INDUCES REG3γ EXPRESSION IN INTESTINAL EPITHELIAL CELLS TO MAINTAIN INTESTINAL HOMEOSTASIS

Crohn’s disease (CD) is characterized by malfunction of immune-regulatory mechanisms with disturbed intestinal mucosal homeostasis and increased activation of mucosal immune cells, leading to abnormal secretion of numerous pro- and anti-inflammatory mediators. MCP2/CCL8 is produced by intestinal epithelial cells and macrophages, and is a critical regulator of mucosal inflammation. NLRC4 is expressed in phagocytes and intestinal epithelial cells and is involved in intestinal homeostasis and host defense. However, no study to date has assessed the circulating levels of NLRC4 and MCP2/CCL8 in patients with CD. The study was aimed to investigate the serum levels of MCP2/CCL8 and NLRC4 in patients with active CD. Sixty-nine patients with active CD and 60 healthy participants were included in the study. Serum levels of NLRC4 and MCP2/CCL8 were determined using an enzyme-linked immunosorbent assay. The median serum NLRC4 levels were lower in the patient group than in the controls (71.02 (range, 46.59–85.51) pg/mL vs. 99.43 (range 83.52–137.79) pg/mL) (P < 0.001). The median serum levels of MCP2/CCL8 were decreased in patients with CD (28.68 (range, 20.16–46.0) pg/mL) compared with the controls (59.96 (range, 40.22–105.59) pg/mL) (P < 0.001). Cut-off points of NLRC4 (<81 pg/mL) and MCP2/CCL8 (<40 pg/mL) showed high sensitivity and specificity for identifying active CD. In conclusion, this is the first study to examine circulating levels of MCP2/CCL8 and NLRC4 in patients with active CD. Our results suggest that serum NLRC4 and MCP2/CCL8 levels may be involved in the pathogenesis of CD and may have a protective effect on intestinal homeostasis and inflammation. Serum levels of MCP2/CCL8 and NLRC4 could be used as a diagnostic tool and therapeutic target for CD.

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Arid1a is essential for intestinal stem cells through Sox9 regulation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1804858116 ◽

2019 ◽

Vol 116 (5) ◽

pp. 1704-1713 ◽

Cited By ~ 5

Author(s):

Yukiko Hiramatsu ◽

Akihisa Fukuda ◽

Satoshi Ogawa ◽

Norihiro Goto ◽

Kozo Ikuta ◽

...

Keyword(s):

Stem Cells ◽

Epithelial Cells ◽

Functional Role ◽

Molecular Mechanisms ◽

Intestinal Epithelial Cells ◽

Lineage Tracing ◽

Intestinal Stem Cells ◽

Intestinal Epithelial ◽

Intestinal Homeostasis ◽

Self Renewal

Inactivating mutations of Arid1a, a subunit of the Switch/sucrose nonfermentable chromatin remodeling complex, have been reported in multiple human cancers. Intestinal deletion of Arid1a has been reported to induce colorectal cancer in mice; however, its functional role in intestinal homeostasis remains unclear. We investigated the functional role of Arid1a in intestinal homeostasis in mice. We found that intestinal deletion of Arid1a results in loss of intestinal stem cells (ISCs), decreased Paneth and goblet cells, disorganized crypt-villous structures, and increased apoptosis in adult mice. Spheroids did not develop from intestinal epithelial cells deficient for Arid1a. Lineage-tracing experiments revealed that Arid1a deletion in Lgr5+ ISCs leads to impaired self-renewal of Lgr5+ ISCs but does not perturb intestinal homeostasis. The Wnt signaling pathway, including Wnt agonists, receptors, and target genes, was strikingly down-regulated in Arid1a-deficient intestines. We found that Arid1a directly binds to the Sox9 promoter to support its expression. Remarkably, overexpression of Sox9 in intestinal epithelial cells abrogated the above phenotypes, although Sox9 overexpression in intestinal epithelial cells did not restore the expression levels of Wnt agonist and receptor genes. Furthermore, Sox9 overexpression permitted development of spheroids from Arid1a-deficient intestinal epithelial cells. In addition, deletion of Arid1a concomitant with Sox9 overexpression in Lgr5+ ISCs restores self-renewal in Arid1a-deleted Lgr5+ ISCs. These results indicate that Arid1a is indispensable for the maintenance of ISCs and intestinal homeostasis in mice. Mechanistically, this is mainly mediated by Sox9. Our data provide insights into the molecular mechanisms underlying maintenance of ISCs and intestinal homeostasis.

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Sa606 P40 REGULATES EPIGENETIC IMPRINTING IN INTESTINAL EPITHELIAL CELLS WHICH EXERTS LONG-LASTING EFFECTS ON MAINTAINING INTESTINAL HOMEOSTASIS

Gastroenterology ◽

10.1016/s0016-5085(21)02062-x ◽

2021 ◽

Vol 160 (6) ◽

pp. S-570-S-571

Author(s):

Yilin Deng ◽

Jessica Williams ◽

D. Brent Polk ◽

Richard M. Peek ◽

Sari Acra ◽

...

Keyword(s):

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Intestinal Homeostasis

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Neutrophils Promote Amphiregulin Production in Intestinal Epithelial Cells through TGF-β and Contribute to Intestinal Homeostasis

The Journal of Immunology ◽

10.4049/jimmunol.1800003 ◽

2018 ◽

Vol 201 (8) ◽

pp. 2492-2501 ◽

Cited By ~ 7

Author(s):

Feidi Chen ◽

Wenjing Yang ◽

Xiangsheng Huang ◽

Anthony T. Cao ◽

Anthony J. Bilotta ◽

...

Keyword(s):

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Intestinal Homeostasis

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Toll-like receptors 2 and 4 modulate intestinal IL-10 differently in ileum and colon

United European Gastroenterology Journal ◽

10.1177/2050640617727180 ◽

2017 ◽

Vol 6 (3) ◽

pp. 446-453 ◽

Cited By ~ 7

Author(s):

Eva Latorre ◽

Elena Layunta ◽

Laura Grasa ◽

Julián Pardo ◽

Santiago García ◽

...

Keyword(s):

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Cell Model ◽

Immune Recognition ◽

Intestinal Epithelial ◽

Intestinal Homeostasis ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Gram Negative Organisms ◽

Tlr4 Activation

Background Inflammatory bowel diseases are consequence of an intestinal homeostasis breakdown in which innate immune dysregulation is implicated. Toll-like receptor (TLR)2 and TLR4 are immune recognition receptors expressed in the intestinal epithelium, the first physical-physiological barrier for microorganisms, to inform the host of the presence of Gram-positive and Gram-negative organisms. Interleukin (IL)-10 is an essential anti-inflammatory cytokine that contributes to maintenance of intestinal homeostasis. Aim Our main aim was to investigate intestinal IL-10 synthesis and release, and whether TLR2 and TLR4 are determinants of IL-10 expression in the intestinal tract. Methods We used Caco-2 cell line as an enterocyte-like cell model, and also ileum and colon from mice deficient in TLR2, TLR4 or TLR2/4 to test the involvement of TLR signaling. Results Intestinal epithelial cells are able to synthesize and release IL-10 and their expression is increased after TLR2 or TLR4 activation. IL-10 regulation seems to be tissue specific, with IL-10 expression in the ileum regulated by a compensation between TLR2 and TLR4 expression, whereas in the colon, TLR2 and TLR4 affect IL-10 expression independently. Conclusions Intestinal epithelial cells could release IL-10 in response to TLR activation, playing an intestinal tissue-dependent and critical intestinal immune role.

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Three-dimensional organization and functional relationships of endocytotic compartments in pig intestinal epithelial cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123283 ◽

1992 ◽

Vol 50 (1) ◽

pp. 576-577

Author(s):

Julian P. Heath ◽

Buford L. Nichols ◽

László G. Kömüves

Keyword(s):

Electron Microscopy ◽

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Three Dimensional ◽

Intestinal Epithelial ◽

Cell Surfaces ◽

Basal Surface ◽

Functional Relationships

The newborn pig intestine is adapted for the rapid and efficient absorption of nutrients from colostrum. In enterocytes, colostral proteins are taken up into an apical endocytotic complex of channels that transports them to target organelles or to the basal surface for release into the circulation. The apical endocytotic complex of tubules and vesicles clearly is a major intersection in the routes taken by vesicles trafficking to and from the Golgi, lysosomes, and the apical and basolateral cell surfaces.Jejunal tissues were taken from piglets suckled for up to 6 hours and prepared for electron microscopy and immunocytochemistry as previously described.

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