Paneth cells in the large intestine in ulcerative colitis

Watson, A. J.; Roy, A. D.

doi:10.1002/path.1700800214

Cited by 66 publications

(46 citation statements)

References 13 publications

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“…These observations may be related to a changing pattern of Paneth cell expression, because the secretion of protective factors by these cells and mucus-producing goblet cells stimulates epithelial cell continuity and mucosal barrier function and provides ␣-defensins, ␤-defensins, and intestinal trefoil factor that inhibit mucosal invasion by enteric bacteria in both small and large intestines (48 -51). Paneth cells are typically absent from the normal colon but may appear in chronic inflammatory diseases of the colon such as ulcerative colitis and Crohn's disease (52,53). Our data demonstrate that they also appear following infection with T. muris and suggest that IL-4 and IL-10 may contribute to Paneth cell development.…”

Section: Discussionmentioning

confidence: 65%

IL-10 Is Critical for Host Resistance and Survival During Gastrointestinal Helminth Infection

Schopf

Hoffmann

Cheever

et al. 2002

The Journal of Immunology

198

168

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Resistance to many intestinal nematodes is dependent on the induction of polarized type 2 cytokine responses, whereas type 1 responses can exacerbate these infections. The contributions of IL-4 and IL-13 to the development of resistance have been well described for a variety of intestinal parasites; however, the role of IL-10 has not been previously investigated. In this study we infected IL-10-, IL-10/IL-4-, IL-10/IL-12-, IL-4-, and IL-12-deficient mice with Trichuris muris to determine whether IL-10 contributes to the development of immunity. Interestingly, T. muris-infected IL-10-, IL-4-, and IL-10/IL-4-deficient mice failed to expel the parasite, and animals deficient in IL-10 displayed marked morbidity and mortality. In contrast, double IL-10/IL-12-deficient mice were completely resistant and mounted a highly polarized type 2 cytokine response, demonstrating that the increased susceptibility of IL-10-deficient mice was dependent on IL-12. Further study suggested that the susceptibility of IL-10- and IL-10/IL-4-deficient mice was probably attributable to a marked increase in type 1 cytokine production in those animals. The mortality observed in T. muris-infected IL-10- and IL-10/IL-4-deficient mice correlated with increased inflammation, loss of Paneth cells, and absence of mucus in the cecum. Interestingly, survival was enhanced in T. muris-infected IL-10/IL-4-deficient mice if a broad spectrum antibiotic was administered, suggesting that an outgrowth of opportunistic bacteria was contributing to the high degree of morbidity and mortality. Overall, these studies reveal a critical role for IL-10 in the polarization of Th2 responses, development of resistance during T. muris infection, and maintenance of barrier function in the colon.

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Section: Discussionmentioning

confidence: 65%

IL-10 Is Critical for Host Resistance and Survival During Gastrointestinal Helminth Infection

Schopf

Hoffmann

Cheever

et al. 2002

The Journal of Immunology

198

168

View full text Add to dashboard Cite

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“…Paneth cell degranulation is an innate immune response that mediates enteric mucosal defense by killing foreign pathogens in the intestinal lumen (43). Paneth cell metaplasia and hyperplasia are stimulated by intestinal inflammation and are signatures of UC (44). However, although Paneth cells are present in the human colon, they are found only in the mouse small intestine.…”

Section: Discussionmentioning

confidence: 99%

Branched Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Protect against Colitis by Regulating Gut Innate and Adaptive Immune Responses

Lee

Moraes‐Vieira

Castoldi

et al. 2016

Journal of Biological Chemistry

125

124

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We recently discovered a structurally novel class of endogenous lipids, branched palmitic acid esters of hydroxy stearic acids (PAHSAs), with beneficial metabolic and anti-inflammatory effects. We tested whether PAHSAs protect against colitis, which is a chronic inflammatory disease driven predominantly by defects in the innate mucosal barrier and adaptive immune system. There is an unmet clinical need for safe and well tolerated oral therapeutics with direct anti-inflammatory effects. Wild-type mice were pretreated orally with vehicle or 5-PAHSA (10 mg/kg) and 9-PAHSA (5 mg/kg) once daily for 3 days, followed by 10 days of either 0% or 2% dextran sulfate sodium water with continued vehicle or PAHSA treatment. The colon was collected for histopathology, gene expression, and flow cytometry. Intestinal crypt fractions were prepared for ex vivo bactericidal assays. Bone marrow-derived dendritic cells pretreated with vehicle or PAHSA and splenic CD4 ؉ T cells from syngeneic mice were co-cultured to assess antigen presentation and T cell activation in response to LPS. PAHSA treatment prevented weight loss, improved colitis scores (stool consistency, hematochezia, and mouse appearance), and augmented intestinal crypt Paneth cell bactericidal potency via a mechanism that may involve GPR120. In vitro, PAHSAs attenuated dendritic cell activation and subsequent T cell proliferation and Th1 polarization. The anti-inflammatory effects of PAHSAs in vivo resulted in reduced colonic T cell activation and pro-inflammatory cytokine and chemokine expression. These anti-inflammatory effects appear to be partially GPR120-dependent. We conclude that PAHSA treatment regulates innate and adaptive immune responses to prevent mucosal damage and protect against colitis. Thus, PAHSAs may be a novel treatment for colitis and related inflammation-driven diseases.Lipids have been a rich source of chemical matter for the development of new medicines (1). Endogenous small-molecule metabolites are another class of natural products made within the human body that have important biological activities (2). For example, the discovery and synthesis of prostaglandins revealed their diverse biological roles as autocrine and paracrine mediators in many tissues. This led to their development as therapeutic agents for a variety of indications ranging from vasodilatation to glaucoma treatment (3-6). More recently, compounds that target the sphingosine 1 receptors are emerging as novel therapeutics for autoimmune diseases (7). Thus, the discovery and characterization of bioactive lipids is of fundamental interest with broad impact. We recently discovered a structurally novel class of lipids, branched fatty acid esters of hydroxy fatty acids (FAHFAs), 6 with anti-diabetic and anti-inflammatory properties (8). These lipids are products of endogenous synthesis in mammalian tissues and are also present in food. There are more than 16 FAHFA families, and each family is distinguished by having a different fatty acid and hydroxy fatty acid composition. Furthermor...

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“…[14][15][16] These functions include stem cell maintenance, proliferation, and differentiation to Paneth cells. 17 Stem cell-related changes in the epithelium in IBD include induction of Paneth cell differentiation in the colon, 18,19 epithelial ulceration, and increased risk of dysplasia (premalignant change) and cancer. 20 The changes to stem cell function in IBD may be regulated by secreted components of the niche, such as Wnt ligands and/or their inhibitors derived from intestinal myofibroblasts.…”

mentioning

confidence: 99%

Expression profiling of Wnt family of genes in normal and inflammatory bowel disease primary human intestinal myofibroblasts and normal human colonic crypt epithelial cells

Hughes

Sablitzky

Mahida

2011

Inflammatory Bowel Diseases

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Human intestinal myofibroblasts expressed a number of Wnt ligands, their receptors, and inhibitors. In contrast, colonic crypt epithelial cells predominantly expressed Wnt receptors. Compared to myofibroblasts isolated from normal colonic mucosa, those affected by UC showed significantly reduced expression of SFRP1. Since reduced SFRP1 expression has been associated with malignancy, low myofibroblast expression of this Wnt inhibitor may be implicated in increased risk of cancer in UC.

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Paneth cells in the large intestine in ulcerative colitis

Cited by 66 publications

References 13 publications

IL-10 Is Critical for Host Resistance and Survival During Gastrointestinal Helminth Infection

IL-10 Is Critical for Host Resistance and Survival During Gastrointestinal Helminth Infection

Branched Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Protect against Colitis by Regulating Gut Innate and Adaptive Immune Responses

Expression profiling of Wnt family of genes in normal and inflammatory bowel disease primary human intestinal myofibroblasts and normal human colonic crypt epithelial cells

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