Long-term exposure from perinatal life to food-grade TiO2 alters intestinal homeostasis and predisposes to food allergy in young mice.

BACKGROUND: Food allergy (FA) is an inappropriate immunological response to food proteins resulting from an impaired induction of oral tolerance. Various early environmental factors can affect the establishment of intestinal homeostasis, predisposing to FA in early life. In this context, we aimed to assess the effect of chronic perinatal exposure to food-grade titanium dioxide (fg-TiO2 ), a common food additive. METHODS: Dams were fed a control versus fg-TiO2 -enriched diet from preconception to weaning, and their progeny received the same diet at weaning. A comprehensive analysis of baseline intestinal and systemic homeostasis was performed in offspring 1 week after weaning by assessing gut barrier maturation and microbiota composition, and local and systemic immune system and metabolome. The effect of fg-TiO2 on the susceptibility of progeny to develop oral tolerance versus FA to cow's milk proteins (CMP) was performed starting at the same baseline time-point, using established models. Sensitization to CMP was investigated by measuring ß-lactoglobulin and casein-specific IgG1 and IgE antibodies, and elicitation of the allergic reaction by measuring mouse mast cell protease (mMCP1) in plasma collected after an oral food challenge. RESULTS: Perinatal exposure to fg-TiO2 at realistic human doses led to an increased propensity to develop FA and an impaired induction of oral tolerance only in young males, which could be related to global baseline alterations in intestinal barrier, gut microbiota composition, local and systemic immunity, and metabolism. CONCLUSIONS: Long-term perinatal exposure to fg-TiO2 alters intestinal homeostasis establishment and predisposes to food allergy, with a clear gender effect.

Moringa oleifera Leaves Protein Enhances Intestinal Permeability by Activating TLR4 Upstream Signaling and Disrupting Tight Junctions.

Changes in intestinal mucosal barrier permeability lead to antigen sensitization and mast cell-mediated allergic reactions, which are considered to play important roles in the occurrence and development of food allergies. It has been suggested that protein causes increased intestinal permeability via mast cell degranulation, and we investigated the effect of camellia Moringa oleifera leaves protein on intestinal permeability and explored its role in the development of food allergies. The current study investigated the effect of M. oleifera leaves protein on intestinal permeability through assessments of transepithelial electrical resistance (TEER) and transmembrane transport of FITC-dextran by Caco-2 cells. The expression levels of Toll-like receptor 4 (TLR4), IL-8, Occludin, Claudin-1, and perimembrane protein family (ZO-1) were detected by real-time PCR and Western blotting. The effect of M. oleifera leaves protein on intestinal permeability was verified in mice in vivo. The serum fluorescence intensity was measured using the FITC-dextran tracer method, and the expression of tight junction proteins was detected using Western blotting. The results showed that M. oleifera leaves protein widened the gaps between Caco-2 cells, reduced transmembrane resistance, and increased permeability. This protein also reduced the mRNA and protein levels of Occludin, Claudin-1, and ZO-1. Animal experiments showed that intestinal permeability was increased, and that the expression of the tight junction proteins Occludin and Claudin-1 were downregulated in mice. This study shows that M. oleifera leaves protein has components that increase intestinal permeability, decrease tight junction protein expression, promote transmembrane transport in Caco-2 cells, and increase intestinal permeability in experimental animals. The finding that M. oleifera leaves active protein increases intestinal permeability suggests that this protein may be valuable for the prevention, diagnosis, and treatment of M. oleifera leaves allergy.

ß-Sitosterol protects against food allergic response in BALB/c mice by regulating the intestinal barrier function and reconstructing the gut microbiota structure.

This study investigated whether ß-sitosterol has anti-allergic activity and explored its potential mechanism, using ovalbumin (OVA) allergic mouse model. Results indicated that supplementation with ß-sitosterol at 5-20 mg kg-1 day-1 for 7 weeks alleviated allergic symptoms and intestinal inflammation, and reduced serum OVA-specific immunoglobulin (Ig) E, IgG and histamine levels in sensitized mice. ß-Sitosterol enhanced physical and biochemical barrier in the intestinal epithelium by upregulating tight junction proteins (claudin-1, occludin, and ZO-1) expression and promoting the secretion of regenerating islet-derived protein IIIγ and secretory IgA in mucous layer. Furthermore, ß-sitosterol administration increased the levels of interleukin 10 and transforming growth factor-ß secreted by regulatory T cells, while reducing T helper 2 cell associated factor levels in intestinal lamina propria. Additionally, the alpha and beta diversity analysis revealed that the structure and diversity of the intestinal flora in the ß-sitosterol group tended to be normalized compared with the model group, and the number of biomarkers was reduced from 32 to 7. Moreover, the altered composition of gut microbiota in allergic mice was also reversed by ß-sitosterol supplementation, characterized by an increase in abundance of Lactobacillaceae and Bifidobacteriaceae and a decrease in abundance of Desulfovibrionaceae. Consequently, ß-sitosterol may prevent FA by ameliorating intestinal barrier function and remodeling the gut microbiota.

Thymic stromal lymphopoietin rather than IL-33 drives food allergy after epicutaneous sensitization to food allergen.

BACKGROUND: A major route of sensitization to food allergen is through an impaired skin barrier. IL-33 and thymic stromal lymphopoietin (TSLP) have both been implicated in epicutaneous sensitization and food allergy, albeit in different murine models. OBJECTIVE: We assessed the respective contributions of TSLP and IL-33 to the development of atopic dermatitis (AD) and subsequent food allergy in TSLP and IL-33 receptor (ST2)-deficient mice using an AD model that does not require tape stripping. METHOD: TSLP receptor (TSLPR)-/-, ST2-/-, and BALB/cJ control mice were exposed to 3 weekly epicutaneous skin patches of one of saline, ovalbumin (OVA), or a combination of OVA and Aspergillus fumigatus (ASP), followed by repeated intragastric OVA challenges and development of food allergy. RESULTS: ASP and/or OVA patched, but not OVA-alone patched, BALB/cJ mice developed an AD-like skin phenotype. However, epicutaneous OVA sensitization occurred in OVA patched mice and was decreased in ST2-/- mice, resulting in lower intestinal mast cell degranulation and accumulation, as well as OVA-induced diarrhea occurrences on intragastric OVA challenges. In TSLPR-/- mice, intestinal mast cell accumulation was abrogated, and no diarrhea was observed. AD was significantly milder in OVA + ASP patched TSLPR-/- mice compared to wild type and ST2-/- mice. Accordingly, intestinal mast cell accumulation and degranulation were impaired in OVA + ASP patched TSLPR-/- mice compared to wild type and ST2-/- mice, protecting TSLPR-/- mice from developing allergic diarrhea. CONCLUSION: Epicutaneous sensitization to food allergen and development of food allergy can occur without skin inflammation and is partly mediated by TSLP, suggesting that prophylactic targeting of TSLP may be useful in mitigating the development of AD and food allergy early in life in at-risk infants.

Avenanthramide Improves Colonic Damage Induced by Food Allergies in Mice through Altering Gut Microbiota and Regulating Hsp70-NF-κB Signaling.

Food allergies can cause intestinal damage that can exacerbate allergic symptoms, and gut microbiota have been shown to influence allergic development. This study was intended to investigate the effects of Avenanthramide (AVA) on colonic damage induced by food allergy and its mechanism. In Exp. 1, AVA administrations alleviated colonic inflammation in mice challenged with ovalbumin, as shown by decreased concentrations of TNF-α, IL-25 and IL-33. Additionally, the AVA supplementations improved intestinal barrier damage by elevating occludin, ZO-1 and claudin-1 levels. Moreover, AVA inhibited NF-κB phosphorylation and enhanced heat shock protein 70 (Hsp70) expression in the colon. In Exp. 2, apoptozole as a Hsp70 inhibitor was used to explore the Hsp70-NF-κB signaling contribution to AVA function. The AVA additions increased the productions of acetate and butyrate, but decreased propionate. Notably, AVA reduced the colonic abundance of propionate-producing microbes such as Muribaculaceae, but elevated butyrate-producing microbes including Roseburia, Blautia, and Lachnospiraceae_NK4A136_group. Microbial alteration could be responsible for the increased butyrate, and thus the up-regulated Hsp70. However, apoptozole treatment eliminated the effects of AVA. Our study revealed that AVA improved colonic injury and inflammation induced by food allergies, and this mechanism may be mediated by the increased microbial-derived butyrate and involved in the Hsp70-NF-κB signaling.

Fucoxanthin Prevents the Ovalbumin-Induced Food Allergic Response by Enhancing the Intestinal Epithelial Barrier and Regulating the Intestinal Flora.

This study aimed to determine whether fucoxanthin alleviated ovalbumin (OVA)-induced food allergy (FA) and explored the possible mechanisms. The results indicated that supplementation with fucoxanthin at 10.0-20.0 mg/kg per day for 7 weeks inhibited food anaphylaxis and the production of immunoglobulin (Ig) E, IgG, histamine, and related cytokines while alleviating allergic symptoms in sensitized mice. Fucoxanthin enhanced the intestinal epithelial barrier by up-regulating tight junction (TJ) protein expression and promoting regenerating islet-derived protein III-gamma (RegIIIγ) and secretory IgA (sIgA) secretion. In addition, fucoxanthin induced the secretion of anti-inflammatory factors (interleukin (IL)-10 and transforming growth factor ß (TGF-ß)) by regulatory T (Treg) cells and decreased the pro-inflammatory factor levels (IL-4, tumor necrosis factor-α (TNF-α), IL-17, and IL-1ß), ameliorating intestinal inflammation. Compared with the model group, beneficial bacteria, such as Lactobacillaceae, increased in the intestinal flora, while pathogenic bacteria like Helicobacteraceae, Desulfovibrionaceae, and Streptococcaceae decreased. Therefore, fucoxanthin may effectively prevent FA by enhancing the intestinal epithelial barrier and reshaping the intestinal flora.

Claudin-1 Mediated Tight Junction Dysfunction as a Contributor to Atopic March.

Atopic march refers to the phenomenon wherein the occurrence of asthma and food allergy tends to increase after atopic dermatitis. The mechanism underlying the progression of allergic inflammation from the skin to gastrointestinal (GI) tract and airways has still remained elusive. Impaired skin barrier was proposed as a risk factor for allergic sensitization. Claudin-1 protein forms tight junctions and is highly expressed in the epithelium of the skin, airways, and GI tract, thus, the downregulation of claudin-1 expression level caused by CLDN-1 gene polymorphism can mediate common dysregulation of epithelial barrier function in these organs, potentially leading to allergic sensitization at various sites. Importantly, in patients with atopic dermatitis, asthma, and food allergy, claudin-1 expression level was significantly downregulated in the skin, bronchial and intestinal epithelium, respectively. Knockdown of claudin-1 expression level in mouse models of atopic dermatitis and allergic asthma exacerbated allergic inflammation, proving that downregulation of claudin-1 expression level contributes to the pathogenesis of allergic diseases. Therefore, we hypothesized that the tight junction dysfunction mediated by downregulation of claudin-1 expression level contributes to atopic march. Further validation with clinical data from patients with atopic march or mouse models of atopic march is needed. If this hypothesis can be fully confirmed, impaired claudin-1 expression level may be a risk factor and likely a diagnostic marker for atopic march. Claudin-1 may serve as a valuable target to slowdown or block the progression of atopic march.

Identification of allergens and allergen hydrolysates by proteomics and metabolomics: A comparative study of natural and enzymolytic bee pollen.

Bee pollen as a plant-derived food is consumed as nutritional/functional supplements by humans. But it might confer foodborne allergenicity in susceptible populations, limiting its extensive application. In this study, five potential allergens including profilin, cystatin, prolamin, expansin, and alcohol dehydrogenase in bee pollen derived from Brassica campestris (BP-Bc), were identified through mass spectrometry-based proteomic analysis. Moreover, different types of enzymes (cellulases, pectases, and papains) serve biological roles in pollen wall breaking and expansion, but also promote allergen release and degradation. Proteomic analysis showed that profilin, cystatin, and alcohol dehydrogenase were significantly reduced in BP-Bc following joint treatment with three enzymes. Metabolomic characterization of potential enzymatic hydrolysates of these significantly-decreased allergens was performed, which showed nine major oligopeptides and six amino acids at significantly higher levels in the enzyme-treated BP-Bc. These findings clarified the culprit responsible for bee pollen allergy and the mechanism of enzymatic desensitization for its further development.

Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils.

Mast cells and basophils have long been implicated in the pathogenesis of IgE-mediated hypersensitivity reactions. They express the high-affinity IgE receptor, FcϵRI, on their surface. Antigen-induced crosslinking of IgE antibodies bound to that receptor triggers a signaling cascade that results in activation, leading to the release of an array of preformed vasoactive mediators and rapidly synthesized lipids, as well as the de novo production of inflammatory cytokines. In addition to bearing activating receptors like FcεRI, these effector cells of allergy express inhibitory ones including FcγR2b, an IgG Fc receptor with a cytosolic inhibitory motif that activates protein tyrosine phosphatases that suppress IgE-mediated activation. We and others have shown that food allergen-specific IgG antibodies strongly induced during the course of oral immunotherapy (OIT), signal via FcγR2b to suppress IgE-mediated mast cell and basophil activation triggered by food allergen challenge. However, the potential inhibitory effects of IgA antibodies, which are also produced in response to OIT and are present at high levels at mucosal sites, including the intestine where food allergens are encountered, have not been well studied. Here we uncover an inhibitory function for IgA. We observe that IgA binds mouse bone marrow-derived mast cells (BMMCs) and peritoneal mast cells. Binding to BMMCs is dependent on calcium and sialic acid. We also found that IgA antibodies inhibit IgE-mediated mast cell degranulation in an allergen-specific fashion. Antigen-specific IgA inhibits IgE-mediated mast cell activation early in the signaling cascade, suppressing the phosphorylation of Syk, the proximal protein kinase mediating FcεRI signaling, and suppresses mast cell production of cytokines. Furthermore, using basophils from a peanut allergic donor we found that IgA binds to basophils and that activation by exposure to peanuts is effectively suppressed by IgA. We conclude that IgA serves as a regulator of mast cell and basophil degranulation, suggesting a physiologic role for IgA in the maintenance of immune homeostasis at mucosal sites.

Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy.

Sustaining higher frequency of mast cells in the allergic lesion site has been recognized. Factors causing high numbers of mast cells in the local tissues are not fully understood yet. RAS signaling plays a role in sustaining certain cell activities. This study is aimed at elucidating the role of RAS activation in the apoptosis resistance induction in mast cells and at employing semaphorin 3A to regulate RAS activities in sensitized mast cells and alleviating the allergic response in the intestine. A food allergy (FA) mouse model was developed. Mast cells were isolated from FA mouse intestinal tissues by flow cytometry. Mast cell apoptosis was assessed by staining with annexin V and propidium iodide. We found that aberrantly higher p21-activated kinase-1 (Pak1) expression in FA mast cells was associated with mast cell aggregation in the intestine. Sensitization increased Pak1 expression and apoptosis resistance in intestinal mast cells. RAS and Pak1 mutually potentiated each other in sensitized mast cells. Semaphorin 3A (sema3A) suppressed the Pak1 expression and RAS activation in mast cells. sema3A restored the apoptosis sensitivity in sensitized mast cells. Administration of sema3A potentiated allergen-specific immunotherapy in experimental FA. In conclusion, mast cells of FA mice showed higher Pak1 expression and high RAS activation status that contributed to apoptosis resistance in mast cells. Administration of sema3A restored the sensitivity to apoptosis inducers and promoted the therapeutic effects of specific immunotherapy on experimental FA.

Effects of fucoidans and alginates from Sargassum graminifolium on allergic symptoms and intestinal microbiota in mice with OVA-induced food allergy.

Food allergy has been one of the main problems threatening people's health in recent years. However, there is still no way to completely cure it at present. Therefore, the development of food allergy related drugs is still necessary. Sargassum graminifolium (SG) is a kind of polysaccharide rich marine brown alga used in food and medicine. Sargassum graminifolium polysaccharides (SGP) is mainly composed of fucoidans and alginic acid. In our study, we compared the activity of fucoidans and alginates from SG against OVA-induced food allergy in a mouse model, observed the regulatory effects of fucoidans and alginates from SG on the intestinal microbiota and summarized the possible role of the intestinal microbiota in the anti-food allergy process because polysaccharides can further act on the body through the intestinal microbiota. The results showed that fucoidans and alginates from SG could relieve the symptoms of allergy, diarrhea and jejunum injury significantly in mice with food allergy (p < 0.05). Furthermore, fucoidans at 500 mg kg-1 could reduce OVA-specific IgE and TNF-α levels significantly in the serum of food allergic mice (p < 0.05), while alginates could only significantly down-regulate serum OVA-specific IgE (p < 0.05). The results also showed that fucoidans had a stronger regulatory effect on the richness and diversity of the intestinal microbiota in food allergic mice compared to alginates at the same dose. In addition, fucoidans at 500 mg kg-1 had the most significant regulatory effect on Firmicutes, Lactobacillus and Alistipes in food allergic mice. These results suggested that fucoidans and alginates might regulate food allergy in mice through different pathways. Together, this study enriched the research on the action of alga-derived polysaccharides against food allergy.

Gastrointestinal fate of food allergens and its relationship with allergenicity.

Food allergens are closely related to their gastrointestinal digestion fate, but the changes in food allergens during digestion and related mechanisms are quite complicated. This review presents in detail digestion models for predicting allergenicity, the fates of food allergens in oral, gastric and duodenal digestion, and the applications of digestomics in mapping IgE-binding epitopes of digestion-resistant peptides. Moreover, this review highlights the structure-activity relationships of food allergens during gastrointestinal digestion. Digestion-labile allergens may share common structural characteristics, such as high flexibility, rendering them easier to be hydrolyzed into small fragments with decreased or eliminated allergenicity. In contrast, the presence of disulfide bonds, tightly wound α-helical structures, or hydrophobic domains in food allergens helps them resist gastrointestinal digestion, stabilizing IgE-binding epitopes, thus maintaining their sensitization. In rare cases, digestion leads to increased allergenicity due to exposure of new epitopes. Finally, the action of the food matrix and processing on the digestion and allergenicity of food allergens as well as the underlying mechanisms was overviewed. The food matrix can directly act on the allergen by forming complexes or new epitopes to affect its gastrointestinal digestibility and thereby alter its allergenicity or indirectly affect the allergenicity by competing for enzymatic cleavage or influencing gastrointestinal pH and microbial flora. Several processing techniques attenuate the allergenicity of food proteins by altering their conformation to improve susceptibility to degradation by digestive enzymes. Given the complexity of food components, the food itself rather than a single allergen should be used to obtain more accurate data for allergenicity assessment. PRACTICAL APPLICATION: The review article will help to understand the relationship between food protein digestion and allergenicity, and may provide fundamental information for evaluating and reducing the allergenicity of food proteins.

Basophil Activation Test Utility as a Diagnostic Tool in LTP Allergy.

Plant-food allergy is an increasing problem, with nonspecific lipid transfer proteins (nsLTPs) triggering mild/severe reactions. Pru p 3 is the major sensitizer in LTP food allergy (FA). However, in vivo and in vitro diagnosis is hampered by the need for differentiating between asymptomatic sensitization and allergy with clinical relevance. The basophil activation test (BAT) is an ex vivo method able to identify specific IgE related to the allergic response. Thus, we aimed to establish the value of BAT in a precise diagnosis of LTP-allergic patients. Ninety-two individuals with peach allergy sensitized to LTP, Pru p 3, were finally included, and 40.2% of them had symptoms to peanut (n = 37). In addition, 16 healthy subjects were recruited. BAT was performed with Pru p 3 and Ara h 9 (peanut LTP) at seven ten-fold concentrations, and was evaluated by flow cytometry, measuring the percentage of CD63 (%CD63+) and CD203c (%CD203chigh) cells, basophil allergen threshold sensitivity (CD-Sens), and area under the dose−response curve (AUC). Significant changes in BAT parameters (%CD63+ and %CD203chigh) were found between the controls and patients. However, comparisons for %CD63+, %CD203chigh, AUC, and CD-Sens showed similar levels among patients with different symptoms. An optimal cut-off was established from ROC curves, showing a significant positive percentage of BAT in patients compared to controls and great values of sensitivity (>87.5%) and specificity (>85%). In addition, BAT showed differences in LTP-allergic patients tolerant to peanut using its corresponding LTP, Ara h 9. BAT can be used as a potential diagnostic tool for identifying LTP allergy and for differentiating peanut tolerance, although neither reactivity nor sensitivity can distinguish the severity of the clinical symptoms.

Analysis of Serum Th2 Cytokines in Infants with Non-IgE Mediated Food Allergy Compared to Healthy Infants.

Background: The aim of this study is to assess the serum values of IL-4, IL-5, IL-10, and IL-13 in a group of infants with non-IgE mediated food allergies treated with a hydrolyzed formula and compare them with a group of healthy peers. Methods: A total of 53 infants aged 1 to 4 months, of which 34 with non-IgE mediated food allergies and 19 healthy infants were enrolled in this study. Infants were eligible if they had gastrointestinal symptoms of food allergy and needed to switch from their initial formula to hydrolyzed formulas with an improvement of symptoms. Controls were fed with either breastmilk or standard formula. Blood samples were taken within one week of a special diet for cases. Interleukinsin in peripheral blood was detected and analyzed using the real-time PCR MAMA method. Fecal calprotectin was evaluated using a quantitative assay. Results: Values of IL-4 and IL-13 were significantly higher in the non-IgE food allergy group compared to the control group (p < 0.05), while IL-5 and IL-10 were significantly lower than the control group (p < 0.05). Fecal calprotectin in the non-IgE food allergy group was significantly higher compared to the control group (p < 0.05). Conclusion: This study provides a theoretical basis that Th2 cytokine expression in infants with a non-IgE mediated food allergy is significantly different than in healthy infants; this finding supports the use of early dietetic treatment with hydrolyzed formulas.

Fish allergens of turbot (Scophthalmus maximus) parvalbumin triggers food allergy via inducing maturation of bone marrow derived dendritic cells and driving Th2 immune response.

Aquatic food allergy has become a key food safety problem and therefore it is urgent to study the mechanism of aquatic food allergy. Turbot parvalbumin (PV) is a major marine food allergen that could cause allergic reactions but the cellular and molecular mechanisms remain to be defined. In this study, we used flow cytometry and ELISA, a coupled co-culture system of dendritic cells and T cells, and revealed that PV could promote the maturation of dendritic cells, mainly by inducing bone marrow-derived dendritic cells (BMDCs) to express MHC II and CD86, and promote the cytokines/chemokines IL-6, IFN-γ, IL-23, and IL-12p70, whereas inhibiting TNF-α expression. Our results suggested that murine BMDCs play a crucial role in the effect of PV on the induction of Th2 responses.

High-Fat Diet-Induced Obesity Aggravates Food Allergy by Intestinal Barrier Destruction and Inflammation.

INTRODUCTION: The increase in high-fat diet (HFD)-induced obesity and food allergy leads to an assumption that the 2 are related. This study aims to (1) systematic verification of HFD-induced obesity aggravates food allergy and (2) explore the correlation and molecular mechanisms of HFD-induced obesity promotes food allergy. METHODS: Female BALB/c mice are divided into the control group (control), the ovalbumin (OVA)-sensitized group (OVA), the HFD-induced obesity group (HFD), and HFD-induced allergic obesity group (HFD + OVA). RESULTS: In vivo data showed that HFD feed enhance clinical symptoms and intestinal mucosa villi shed on allergic mice. Moreover, we found that HFD and OVA irritation enhanced levels of mast cell degranulation and Th2 humoral response. Additionally, Western blot analysis showed the potentiation of peroxisome proliferator-activated receptor γ (PPAR γ) remarkably reduced on intestinal in HFD and OVA group, thereby inhibiting the expression of nuclear factor kappa B (NF-κB)/PPAR γ signal the phosphorylation of NF-κB P65. CONCLUSIONS: Overall, our results suggest that HFD-induced obesity is a potential risk factor for food allergy, which related to intestinal barrier destruction and inflammation through the PPAR γ/NF-κB signaling pathway.

Dermatan sulfate and chondroitin sulfate from Lophius litulon alleviate the allergy sensitized by major royal jelly protein 1.

The objective of the present study was to explore the desensitization effect of dermatan sulfate (DS) and chondroitin sulfate (CS) from Lophius litulon (Ll) on mice sensitized by major royal jelly protein 1 (MRJP1). First, the affinity between six glycosaminoglycans and the MRJP1 polyclonal antibody was measured by the ELISA method. Lophius litulon dermatan sulfate (Ll DS) and Lophius litulon chondroitin sulfate (Ll CS) were selected due to their highest binding affinity. Second, the molecular docking method was used to explore the interaction between Ll DS and MRJP1 and Ll CS and MRJP1. The results showed that Ll DS and Ll CS combined with MRJP1 successfully, which meant a potential function of relieving the MRJP1-caused allergy. Finally, the MRJP1-sensitized mice model was established and confirmed that Ll DS and Ll CS had the desensitization ability to relieve MRJP1-induced allergic symptoms. To validate the conclusion, the relief of allergic symptoms in mice was observed. The production of total IgE, MRJP1-specific IgE and histamine was measured. The desensitization mechanism was further studied by measuring cytokines (IL-4 and IFN-γ) from splenocytes stimulated with MRJP1 in vitro. Based on in vivo and in vitro experiments, it was confirmed that Ll DS and Ll CS have the ability to alleviate MRJP1-induced allergic symptoms, which proposes a potential candidate material against IgE-mediated food allergy.

Oxytocin suppresses epithelial cell-derived cytokines production and alleviates intestinal inflammation in food allergy.

Food allergy is a growing healthcare problem worldwide, but prophylactic options and regulatory therapies are limited. Oxytocin (OXT), conventionally acknowledged as a hormone, was recently proven to have potent anti-inflammatory and immunomodulatory activities in certain diseases. Here, we reported the novel function and its underlying mechanisms of OXT on food allergy in vivo and in vitro. We showed that the levels of OXT were elevated in ovalbumin (OVA)-allergic mice and patients with food allergy. In HT-29 cells, OXT inhibited the production of the epithelial cell-derived cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33 by suppressing NF-κB signaling, in which ß-arrestin2 participated. These functions of OXT were abolished by oxytocin receptor (OXTR) depletion. Treating OVA-induced BALB/c mice with OXT suppressed TSLP, IL-25 and IL-33 production and attenuated systemic anaphylaxis and intestinal inflammation. OXTR-/- mice showed extreme increases in TSLP, IL-25 and IL-33 levels as well as severe systemic anaphylaxis and intestinal inflammation. In conclusion, through OXTRs, OXT has a promising antiallergic effect on experimental food allergy by suppressing epithelial TSLP, IL-25 and IL-33 production via inhibiting NF-κB signaling and upregulating ß-arrestin2 expression. Our study provides a new therapeutic perspective for food allergy in humans.

Sphingoid base in pineapple glucosylceramide suppresses experimental allergy by binding leukocyte mono-immunoglobulin-like receptor 3.

BACKGROUND: The increase in patients suffering from type I hypersensitivity, including hay fever and food allergy, is a serious public health issue around the world. Recent studies have focused on allergy prevention by food factors with fewer side effects. The purpose of this study was to evaluate the effect of dietary glucosylceramide from pineapples (P-GlcCer) on type I hypersensitivity and elucidate mechanisms. RESULTS: Oral administration of P-GlcCer inhibited ear edema in passive cutaneous anaphylaxis reaction. In a Caco-2/RBL-2H3 co-culture system, P-GlcCer inhibited ß-hexosaminidase release from RBL-2H3 cells. The direct treatment of P-GlcCer on RBL-2H3 did not affect ß-hexosaminidase release, but sphingoid base moiety of P-GlcCer did. These results predicted that sphingoid base, a metabolite of P-GlcCer, through the intestine inhibited type I hypersensitivity by inhibiting mast cell degranulation. In addition, the inhibitory effects of P-GlcCer on ear edema and degranulation of RBL-2H3 cells were canceled by pretreatment of leukocyte mono-immunoglobulin-like receptor 3 (LMIR3)-Fc, which can block LMIR3-mediated inhibitory signals. CONCLUSION: It was demonstrated that a sphingoid base, one of the metabolites of P-GlcCer, may inhibit mast cell degranulation by binding to LMIR3. The oral administration of P-GlcCer is a novel and attractive food factor that acts directly on mast cells to suppress allergy. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.