scholarly journals Role of PAR1 in Food Allergies

2020 ◽  
Vol 3 ◽  
Author(s):  
Jennifer Garcia ◽  
Lauren Buelow ◽  
Joan Cook-Mills
Keyword(s):  
Food Allergy ◽  
Skin Barrier ◽  
Food Allergies ◽  
Neonatal Mice ◽  
Signaling Mechanisms ◽  
Skin Keratinocytes ◽  
Potential Impact ◽  
Fungal Allergen ◽  
Deficient Mice

Background and Hypothesis:  The prevalence of food allergies continues to rise. In a mouse model, food allergy to peanuts develops in flaky tail mice with skin barrier mutations and exposure to peanut (PNE) and Alternaria Alternata (fungal allergen, Alt) on the skin. In the skin, keratinocytes respond to proteases in allergens through protease activating receptor 1 (PAR1). Blocking PAR1 decreased the severity of viral induced inflammation in mice. Whether PAR1 has a major role in food allergies has not been investigated. We tested the hypothesis that blocking PAR1 would halt the development of food allergy to peanuts in neonatal mice.    Project Methods:  In our studies, pups were injected intradermally (i.d.) with a PAR1 antagonist and then treated with PNE/Alt. In another group, pups received i.d. injections of a PAR1 agonist and then treated with PNE only. Control groups received allergens only. Pups were treated and skin sensitized 5 times every 3-4 days. Forty-eight hours after the last treatment, pups were challenged with PNE through oral gavage, and temperatures were recorded every 15-30 minutes for 3 hours. Skin, ileum, and jejunum samples were collected and used for qPCR to determine the expression of inflammatory mediators. Plasma serum was used for analysis of anti-PNE specific antibodies by ELISA.      Results:   PAR1 antagonist blocked anaphylaxis in allergic mice sensitized with PNE and Alt. PAR1 agonist is sufficient to induce anaphylaxis in mice sensitized with PNE only.     Conclusion and Potential Impact:  This study demonstrates that PAR1 is involved in the development of food allergies, where blocking the receptor blocked food allergies in neonatal mice. The signaling mechanisms and activators of PAR1 need further studies, using PAR1 deficient mice. This novel pathway may lead to therapies to stop the development of food allergies. 

scholarly journals Epicutaneous sensitization. what do we know?

2022 ◽  
Vol 20 (4) ◽  
pp. 180-192
Author(s):  
G. A. Novik ◽  
M. V. Zhdanova ◽  
A. S. Demidova
Keyword(s):  
Food Allergy ◽  
Web Of Science ◽  
Citation Index ◽  
Experimental Studies ◽  
Skin Barrier ◽  
Relevant Information ◽  
Food Allergies ◽  
Skin Response ◽  
Epicutaneous Sensitization

Background. According to the currently existing hypothesis, epicutaneous sensitization is one of the leading mechanisms in the development of food allergy.The aim of this review was to analyze immune mechanisms in epicutaneous sensitization and the role of skin barrier impairment.We performed a literature search using PubMed, UpToDate, Web of Science, and Scopus databases by the key words: epicutaneous sensitization, atopic dermatitis, skin barrier impairment, food allergy. Articles were to be in open access and present the most relevant information on the topic. Studies were selected by the largest sample size and the highest citation index. Once publications were identified, they were reviewed by all the authors to select the studies that specifically addressed the theme of the review. A total of 101 publications from 1998–2000 were included in the study.This review article discusses the data of experimental studies, sets out modern ideas about the hypothesis of a double exposure to an allergen, and presents research data proving the clinical significance of epicutaneous sensitization in relation to food allergy. Knowledge about the mechanisms of epicutaneous sensitization development is necessary to elaborate strategies for prevention of food allergy. One of the modern trends in prevention is the use of emollients, which are supposed to restore the skin response. However, studies on preventive intake of emollients do not present a similar viewpoint.There is not enough evidence for or against the mechanism of epicutaneous sensitization as an indispensable condition for the formation of food allergies. Further research in this area is required. 

scholarly journals Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition

2018 ◽  
Vol 115 (12) ◽  
pp. E2801-E2810 ◽  
Author(s):  
Emanuele Giurisato ◽  
Qiuping Xu ◽  
Silvia Lonardi ◽  
Brian Telfer ◽  
Ilaria Russo ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Signal Transducer ◽  
Targeted Interventions ◽  
Proinflammatory Mediators ◽  
Signaling Mechanisms ◽  
Transcriptional Switch ◽  
Macrophage Polarity ◽  
Transcription 3 ◽  
Deficient Mice

Owing to the prevalence of tumor-associated macrophages (TAMs) in cancer and their unique influence upon disease progression and malignancy, macrophage-targeted interventions have attracted notable attention in cancer immunotherapy. However, tractable targets to reduce TAM activities remain very few and far between because the signaling mechanisms underpinning protumor macrophage phenotypes are largely unknown. Here, we have investigated the role of the extracellular-regulated protein kinase 5 (ERK5) as a determinant of macrophage polarity. We report that the growth of carcinoma grafts was halted in myeloid ERK5-deficient mice. Coincidentally, targeting ERK5 in macrophages induced a transcriptional switch in favor of proinflammatory mediators. Further molecular analyses demonstrated that activation of the signal transducer and activator of transcription 3 (STAT3) via Tyr705 phosphorylation was impaired in erk5-deleted TAMs. Our study thus suggests that blocking ERK5 constitutes a treatment strategy to reprogram macrophages toward an antitumor state by inhibiting STAT3-induced gene expression.

Non-IgE Mediated Food Allergy

2020 ◽  
Vol 16 (2) ◽  
pp. 95-105
Author(s):  
Antonella Cianferoni
Keyword(s):  
Food Allergy ◽  
Eosinophilic Esophagitis ◽  
Allergic Diseases ◽  
Food Allergies ◽  
Food Protein ◽  
Ige Mediated ◽  
Food Challenges ◽  
Allergic Proctocolitis ◽  
Eosinophilic Disorders

Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in western countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody– mediated immune responses, there is an increasing recognition of cell-mediated disorders, such as eosinophilic esophagitis and food protein–induced enterocolitis. Non-IgE-Mediated gastrointestinal food allergies are a heterogeneous group of food allergies in which there is an immune reaction against food but the primary pathogenesis is not a production of IgE and activation of mast cells and basophils. Those diseases tend to affect mainly the gastrointestinal tract and can present as acute (FPIES) or chronic reaction, such as Eosinophilic Esophagitis (EoE), Food Protein-Induced Allergic Proctocolitis (FPIAP). The role of food allergy in Non-EoE gastrointestinal Eosinophilic disorders (Non- EoE EGID) is poorly understood. In some diseases like EoE, T cell seems to play a major role in initiating the immunological reaction against food, however, in FPIES and FPIAP, the mechanism of sensitization is not clear. Diagnosis requires food challenges and/or endoscopies in most of the patients, as there are no validated biomarkers that can be used for monitoring or diagnosis of Non-IgE mediated food allergies. The treatment of Non-IgE food allergy is dependent on diet (FPIES, and EoE) and/or use of drugs (i.e. steroids, PPI) in EoE and Non-EoE EGID. Non-IgE mediated food allergies are being being investigated.

scholarly journals Prevention of Food Allergy: The Significance of Early Introduction

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 323 ◽  
Author(s):  
Pasquale Comberiati ◽  
Giorgio Costagliola ◽  
Sofia D’Elios ◽  
Diego Peroni
Keyword(s):  
Clinical Trials ◽  
Food Allergy ◽  
Total Duration ◽  
Food Allergies ◽  
Preventive Strategy ◽  
Food Allergens ◽  
High Quality ◽  
Early Introduction ◽  
Potential Food

Over the last two decades, the prevalence of food allergies has registered a significant increase in Westernized societies, potentially due to changes in environmental exposure and lifestyle. The pathogenesis of food allergies is complex and includes genetic, epigenetic and environmental factors. New evidence has highlighted the role of the intestinal microbiome in the maintenance of the immune tolerance to foods and the potential pathogenic role of early percutaneous exposure to allergens. The recent increase in food allergy rates has led to a reconsideration of prevention strategies for atopic diseases, mainly targeting the timing of the introduction of solid foods into infants’ diet. Early recommendation for high atopy risk infants to delay the introduction of potential food allergens, such as cow’s milk, egg, and peanut, until after the first year of life, has been rescinded, as emerging evidence has shown that these approaches are not effective in preventing food allergies. More recently, high-quality clinical trials have suggested an opposite approach, which promotes early introduction of potential food allergens into infants’ diet as a means to prevent food allergies. This evidence has led to the production of new guidelines recommending early introduction of peanut as a preventive strategy for peanut allergy. However, clinical trials investigating whether this preventive dietary approach could also apply to other types of food allergens have reported ambiguous results. This review focuses on the latest high-quality evidence from randomized controlled clinical trials examining the timing of solid food introduction as a strategy to prevent food allergies and also discusses the possible implications of early complementary feeding on both the benefits and the total duration of breastfeeding.

scholarly journals Primary Prevention of Food Allergy—Environmental Protection beyond Diet

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2025
Author(s):  
Hanna Sikorska-Szaflik ◽  
Barbara Sozańska
Keyword(s):  
Food Allergy ◽  
Primary Prevention ◽  
Environmental Factors ◽  
Current Knowledge ◽  
Food Allergies ◽  
Allergy Prevention ◽  
Delivery Mode ◽  
Effective Prevention ◽  
Inhalant Allergens

A food allergy is a potentially life-threatening disease with a genetic and environmental background. As its prevalence has increased significantly in recent years, the need for its effective prevention has been emphasized. The role of diet modifications and nutrients in food allergy reduction has been extensively studied. Much less is known about the role of other environmental factors, which can influence the incidence of this disease. Changes in neonates gut microbiome by delivery mode, animal contact, inhalant allergens, oral and then cutaneous allergen exposure, air pollution, smoking, infections and vaccinations can be the potential modifiers of food allergy development. There is some data about their role as the risk or preventive factors, but yet the results are not entirely consistent. In this paper we present the current knowledge about their possible role in primary prevention of food allergies. We discuss the mechanisms of action, difficulties in designing accurate studies about food allergy and the potential biases in interpreting the connection between environmental factors and food allergy prevention. A better understanding of the role of environmental factors in food allergies development may help in implementing practical solutions for food allergy primary prevention in the future.

Non-IgE Mediated Food Allergy

2020 ◽  
Vol 16 (2) ◽  
pp. 95-105
Author(s):  
Antonella Cianferoni
Keyword(s):  
Food Allergy ◽  
Eosinophilic Esophagitis ◽  
Allergic Diseases ◽  
Food Allergies ◽  
Food Protein ◽  
Ige Mediated ◽  
Food Challenges ◽  
Allergic Proctocolitis ◽  
Eosinophilic Disorders

: Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in western countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody– mediated immune responses, there is an increasing recognition of cell-mediated disorders, such as eosinophilic esophagitis and food protein–induced enterocolitis. Non-IgE-Mediated gastrointestinal food allergies are a heterogeneous group of food allergies in which there is an immune reaction against food but the primary pathogenesis is not a production of IgE and activation of mast cells and basophils. : Those diseases tend to affect mainly the gastrointestinal tract and can present as acute (FPIES) or chronic reaction, such as Eosinophilic Esophagitis (EoE), Food Protein-Induced Allergic Proctocolitis (FPIAP). The role of food allergy in Non-EoE gastrointestinal Eosinophilic disorders (Non- EoE EGID) is poorly understood. : In some diseases like EoE, T cell seems to play a major role in initiating the immunological reaction against food, however, in FPIES and FPIAP, the mechanism of sensitization is not clear. : Diagnosis requires food challenges and/or endoscopies in most of the patients, as there are no validated biomarkers that can be used for monitoring or diagnosis of Non-IgE mediated food allergies. : The treatment of Non-IgE food allergy is dependent on diet (FPIES, and EoE) and/or use of drugs (i.e. steroids, PPI) in EoE and Non-EoE EGID. : Non-IgE mediated food allergies are being being investigated.

scholarly journals Sex Disparity in Food Allergy: Evidence from the PubMed Database

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Caleb Kelly ◽  
Venu Gangur
Keyword(s):  
Food Allergy ◽  
Food Allergies ◽  
Female Ratio ◽  
Immune Mediated ◽  
Pubmed Database ◽  
Male Female Ratio ◽  
Ige Mediated ◽  
Sex Disparity ◽  
The Relationship

Food allergies are potentially fatal immune-mediated disorders that are growing globally. The relationship between sex and food allergy remains incompletely understood. Here we tested the hypothesis that, should sex influence the clinical response to food allergens, this would be reflected by a sex disparity in published studies of food allergy. We performed a systematic search of the PubMed literature for IgE-mediated allergy to 11 allergenic foods of international regulatory importance. No date restriction was used and only articles in English were considered. Of the 4744 articles retrieved, 591 met the inclusion criteria representing 17528 subjects with food allergies. Whereas among children with food allergies, 64.35% were males and 35.65% were females (male/female ratio, 1.80), among adults 34.82% were males and 65.18% were females (male/female ratio, 0.53). Consequently, these data argue that there is need for further investigation to define the role of sex in the pathogenesis of food allergy.

scholarly journals The Role of Skin Barrier in the Pathogenesis of Food Allergy

Children ◽  
2015 ◽  
Vol 2 (3) ◽  
pp. 382-402 ◽  
Author(s):  
Neema Izadi ◽  
Minnelly Luu ◽  
Peck Ong ◽  
Jonathan Tam
Keyword(s):  
Food Allergy ◽  
Skin Barrier

scholarly journals Mechanisms for Alternaria alternata Function in the Skin During Induction of Peanut Allergy in Neonatal Mice With Skin Barrier Mutations

2021 ◽  
Vol 2 ◽  
Author(s):  
Lauren M. Buelow ◽  
Akihiko Hoji ◽  
Kiet Tat ◽  
Lindsay M. Schroeder-Carter ◽  
Daniela J. Carroll ◽  
...  
Keyword(s):  
Food Allergy ◽  
Alternaria Alternata ◽  
Peanut Allergy ◽  
Skin Barrier ◽  
Cell Types ◽  
Intradermal Injection ◽  
Oncostatin M ◽  
Skin Sensitization ◽  
Neonatal Mice ◽  
Genes Encoding

Neonatal mice with heterozygous mutations in genes encoding the skin barrier proteins filaggrin and mattrin (flaky tail mice [FT+/−]) exhibit oral peanut-induced anaphylaxis after skin sensitization. As we have previously reported, sensitization in this model is achieved via skin co- exposure to the environmental allergen Alternaria alternata (Alt), peanut extract (PNE), and detergent. However, the function of Alt in initiation of peanut allergy in this model is little understood. The purpose of this study was to investigate candidate cytokines induced by Alt in the skin and determine the role of these cytokines in the development of food allergy, namely oncostatin M (Osm), amphiregulin (Areg), and IL-33. RT-qPCR analyses demonstrated that skin of FT+/− neonates expressed Il33 and Osm following Alt or Alt/PNE but not PNE exposure. By contrast, expression of Areg was induced by either Alt, PNE, or Alt/PNE sensitization in FT+/− neonates. In scRNAseq analyses, Osm, Areg, and Il33 were expressed by several cell types, including a keratinocyte cluster that was expanded in the skin of Alt/PNE-exposed FT+/− pups as compared to Alt/PNE-exposed WT pups. Areg and OSM were required for oral PNE-induced anaphylaxis since anaphylaxis was inhibited by administration of neutralizing anti-Areg or anti-OSM antibodies prior to each skin sensitization with Alt/PNE. It was then determined if intradermal injection of recombinant IL33 (rIL33), rAreg, or rOSM in the skin could substitute for Alt during skin sensitization to PNE. PNE skin sensitization with intradermal rIL33 was sufficient for oral PNE-induced anaphylaxis, whereas skin sensitization with intradermal rAreg or rOSM during skin exposure to PNE was not sufficient for anaphylaxis to oral PNE challenge. Based on these studies a pathway for IL33, Areg and OSM in Alt/PNE sensitized FT+/− skin was defined for IgE induction and anaphylaxis. Alt stimulated two pathways, an IL33 pathway and a pathway involving OSM and Areg. These two pathways acted in concert with PNE to induce food allergy in pups with skin barrier mutations.

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