Cyclooxygenase-2 in mucosal DC mediates induction of regulatory T cells in the intestine through suppression of IL-4

Broere, Femke; Pré, M. Fleur du; Berkel, L.M. van; Garssen, Johan; Schmid-Weber, C.B.; Lambrecht, Bart N.; Hendriks, R.; Nieuwenhuis, E. E. S.; Kraal, Georg; Samsom, Janneke N.

doi:10.1038/mi.2009.2

Cited by 43 publications

(42 citation statements)

References 53 publications

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“…12,46 anti-inflammatory cytokines and mediators, such as interleukin (iL) -4, -5, -10, -13 and transforming-growth-factor-β (tGFβ), are released and these molecules help maintain the healthy balance of the intestinal mucosa. 47 tolerogenic dcs also inhibit pro-inflammatory responses mediated by th1 and th17 cells. 48 toll-like receptor (tLr and green lightning) signaling pathways induce upregulation of antimicrobial peptides and chemoattractants, promote iec survival (by activation of anti-apoptotic genes) and help maintain the mucosal barrier.…”

Section: The Remarkable Adaptation Of the Colonic Mucosa To Toll-likementioning

confidence: 99%

Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice

Nagy‐Szakal

Kellermayer²

2011

Gut Microbes

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Section: The Remarkable Adaptation Of the Colonic Mucosa To Toll-likementioning

confidence: 99%

Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice

Nagy‐Szakal

Kellermayer²

2011

Gut Microbes

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“…Additionally, the conversion of naive T cells into Foxp3 + Tregs is directly mediated by regulatory dendritic cells (DCs) that express increased levels of cyclooxygenase (COX)-2, IL-10, TGF-b, or IDO (28,29).…”

Section: Converts Naive T Cells Into Foxp3mentioning

confidence: 99%

Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson’s Disease

Chung

Lee

et al. 2015

The Journal of Immunology

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Foxp3-expressing CD4+ regulatory T cells (Tregs) are vital for maintaining immune tolerance in animal models of various immune diseases. In the present study, we demonstrated that bee venom phospholipase A2 (bvPLA2) is the major BV compound capable of inducing Treg expansion and promotes the survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. We associated this neuroprotective effect of bvPLA2 with microglial deactivation and reduction of CD4+ T cell infiltration. Interestingly, bvPLA2 had no effect on mice depleted of Tregs by injecting anti-CD25 Ab. This finding indicated that Treg-mediated modulation of peripheral immune tolerance is strongly involved in the neuroprotective effects of bvPLA2. Furthermore, our results showed that bvPLA2 directly bound to CD206 on dendritic cells and consequently promoted the secretion of PGE2, which resulted in Treg differentiation via PGE2 (EP2) receptor signaling in Foxp3−CD4+ T cells. These observations suggest that bvPLA2-CD206-PGE2-EP2 signaling promotes immune tolerance through Treg differentiation and contributes to the prevention of various neurodegenerative diseases, including Parkinson’s disease.

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“…SA as well as aspirin prevents prostaglandin formation by inhibiting cyclooxygenases (COX). Recently it was shown that the COX-2 in mucosal dendritic cells may be involved in induction of oral tolerance to dietary antigen via mediating activation of regulatory T cells (Broere et al, 2009). It may suggest an effect of SA different from that of oil emulsion in the sensitization process.…”

Section: Discussionmentioning

confidence: 99%

Effective induction of oral anaphylaxis to ovalbumin in mice sensitized by feeding of the antigen with aid of oil emulsion and salicylate

et al. 2012

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INTRODUCTIONThe potential allergenicity of novel proteins introduced into genetically engineered crops and that of proteins generated during the biotechnological process of food production is an important issue for the evaluation for safety of the food crops and products. Many approaches for assessing the allergenicity of such proteins have been proposed; these can be broadly classified into four areas, namely, the analysis of protein structure to predict allergenicity, serum screening of allergic proteins, new animal models, and proteomics (Selgrade et al., 2009;Ahuja et al., 2010).The biochemical approaches for the assessment of allergenic proteins are grounded on comparisons of the serologic identity of the novel protein with human allergens, taking into account factors such as structural similarity, amino acid sequence homology, resistance to proteolytic digestion in a simulated gastric fluid, and immunochemical reactivity with serum of subjects with allergy (Ladics, 2008). Although such investigations provide important information, they do not directly assess the inherent sensitizing potential of proteins. Animal models of food allergy are required for evaluating the sensitizing potential of allergenic proteins and to investigate mechanisms of food allergy. It is generally recognized that it is hard to reproduce food allergy in animals by oral feeding of a model allergenic protein at ABSTRACT -It is important to evaluate the ability of novel proteins in food crops and products to elicit potentially harmful immunologic responses, including allergic hypersensitivity. We developed a novel mouse model of food allergy involving an oral challenge of a protein antigen after feeding of the antigen in combination with modulating factors often ingested in daily life, namely, dietary oil emulsion and salicylate. In the model, BALB/c mice were sensitized orally for three weeks with ovalbumin (OVA) in linoleic acid/lecithin emulsion, followed immediately by intraperitoneal injection of sodium salicylate. At the end of the sensitization, the incidence of mice positive for serum OVA-specific IgG1 but not IgE had significantly increased in the combined-sensitization group. After the 3-week sensitization, a single or double oral challenge with OVA effectively and significantly caused severe anaphylaxis, as compared with the groups sensitized with OVA in the emulsion or the vehicle alone. Moderate increase of plasma histamine and intestinal abnormality in histology was found only in the combined-sensitization group. Anaphylaxis symptoms in the sensitized mice were induced more by oral challenge than by intravenous challenge, suggesting a critical role for the mucosal system. This is the first model for successful induction of oral anaphylaxis in mice sensitized by feeding of food protein without adjuvant. It will be useful to elucidate the mechanism of food allergy and to detect modulating factors of oral allergy at sensitization using this model, which simulates real life conditions.

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Cyclooxygenase-2 in mucosal DC mediates induction of regulatory T cells in the intestine through suppression of IL-4

Cited by 43 publications

References 53 publications

Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice

Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice

Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson’s Disease

Effective induction of oral anaphylaxis to ovalbumin in mice sensitized by feeding of the antigen with aid of oil emulsion and salicylate

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