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International Journal of Molecular... Dec 2023Allergic rhinitis (AR) is a common pathological condition in otorhinolaryngology. Its prevalence has been increasing worldwide and is becoming a major burden to the... (Review)
Review
Allergic rhinitis (AR) is a common pathological condition in otorhinolaryngology. Its prevalence has been increasing worldwide and is becoming a major burden to the world population. Dendritic cells (DCs) are typically activated and matured after capturing, phagocytosing, and processing allergens during the immunopathogenesis of AR. In addition, the process of DC activation and maturation is accompanied by the production of exosomes, which are cell‑derived extracellular vesicles (EVs) that can carry proteins, lipids, nucleic acids, and other cargoes involved in intercellular communication and material transfer. In particular, DC‑derived exosomes (Dex) can participate in allergic immune responses, where the biological substances carried by them can have potentially important implications for both the pathogenesis and treatment of AR. Dex can also be exploited to carry anti‑allergy agents to effectively treat AR. This provides a novel method to explore the pathogenesis of and treatment strategies for AR further. Therefore, the present review focuses on the origin, composition, function, and biological characteristics of DCs, exosomes, and Dex, in addition to the possible relationship between Dex and AR.
Topics: Humans; Exosomes; Rhinitis, Allergic; Allergens; Extracellular Vesicles; Dendritic Cells
PubMed: 37888754
DOI: 10.3892/ijmm.2023.5320 -
The Journal of Allergy and Clinical... Dec 2023Exposure to insects used in pet food, scientific research, or live fish bait can cause an occupational allergy. The recent shift toward enhanced insect production for...
BACKGROUND
Exposure to insects used in pet food, scientific research, or live fish bait can cause an occupational allergy. The recent shift toward enhanced insect production for human consumption and animal feed will likely expose more employees.
OBJECTIVE
To investigate sensitization and symptoms in employees exposed to edible insects in Flanders.
METHODS
Fifteen insect-exposed employees were recruited and sensitization was explored by skin prick test, basophil activation test, and immunoblotting. Lung function, FeNO, histamine provocation, and sputum induction were studied. Airborne dust sampling was performed and proteins were studied by silver stain and immunoblotting.
RESULTS
Sixty percent of employees self-reported upper respiratory tract symptoms related to insect exposure. Ten employees (71.4%) had a positive histamine provocation test concentration causing a 20% drop in FEV1 less than 8 mg/mL and four (26.7%) had FeNO levels above 25 ppb. Four employees (30.7%) had a positive skin prick test for at least one insect, and seven (58.3%) had a positive basophil activation test. In eight participants with insect sensitization, four (50%) had co-occurring house dust mite sensitization. Two participants had strong IgE binding to a 50-kDa migratory locust allergen, one to a 25-kDa mealworm allergen, and one to mealworm α-amylase. In one center, facility adjustment resulted in a substantial decrease in the inhalable dust fraction.
CONCLUSIONS
Insect exposure leads to high levels of sensitization among employees. Most employees reported symptoms of the upper respiratory system, and two-thirds of employees had bronchial hyperreactivity. Prevention and health surveillance will be important in the developing insect-rearing industry.
Topics: Animals; Humans; Edible Insects; Histamine; Hypersensitivity; Allergens; Dust; Skin Tests
PubMed: 37543086
DOI: 10.1016/j.jaip.2023.07.039 -
Frontiers in Immunology 2023Prophylactic strategies to prevent the development of allergies by establishing tolerance remain an unmet medical need. We previously reported that the transfer of...
INTRODUCTION
Prophylactic strategies to prevent the development of allergies by establishing tolerance remain an unmet medical need. We previously reported that the transfer of autologous hematopoietic stem cells (HSC) expressing the major timothy grass pollen allergen, Phl p 5, on their cell surface induced allergen-specific tolerance in mice. In this study, we investigated the ability of allergen-expressing immune cells (dendritic cells, CD4 T cells, CD8 T cells, and CD19 B cells) to induce allergen-specific tolerance in naive mice and identified CD19 B cells as promising candidates for allergen-specific cell therapy.
METHODS
For this purpose, CD19 B cells were isolated from Phl p 5-transgenic BALB/c mice and transferred to naive BALB/c mice, pre-treated with a short course of rapamycin and an anti-CD40L antibody. Subsequently, the mice were subcutaneously sensitized three times at 4-week intervals to Phl p 5 and Bet v 1 as an unrelated control allergen. Allergen-expressing cells were followed in the blood to monitor molecular chimerism, and sera were analyzed for Phl p 5- and Bet v 1-specific IgE and IgG levels by RBL assay and ELISA, respectively. allergen-induced lung inflammation was measured by whole-body plethysmography, and mast cell degranulation was determined by skin testing.
RESULTS
The transfer of purified Phl p 5-expressing CD19 B cells to naive BALB/c mice induced B cell chimerism for up to three months and prevented the development of Phl p 5-specific IgE and IgG antibody responses for a follow-up period of 26 weeks. Since Bet v 1 but not Phl p 5-specific antibodies were detected, the induction of tolerance was specific for Phl p 5. Whole-body plethysmography revealed preserved lung function in CD19 B cell-treated mice in contrast to sensitized mice, and there was no Phl p 5-induced mast cell degranulation in treated mice.
DISCUSSION
Thus, we demonstrated that the transfer of Phl p 5-expressing CD19 B cells induces allergen-specific tolerance in a mouse model of grass pollen allergy. This approach could be further translated into a prophylactic regimen for the prevention of IgE-mediated allergy in humans.
Topics: Humans; Mice; Animals; Allergens; CD8-Positive T-Lymphocytes; Immunoglobulin E; Hypersensitivity; Mice, Transgenic; Adoptive Transfer; Immunoglobulin G
PubMed: 38077381
DOI: 10.3389/fimmu.2023.1286638 -
Acta Bio-medica : Atenei Parmensis Aug 2023Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous... (Review)
Review
BACKGROUND
Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous immunotherapy (SCIT) with high biological power allergen extracts caused a number of severe systemic reactions and also fatalities in the UK and the US, resulting in its limitation and in the introduction of other routes of administration. A decisive advance for SCIT safety was understanding that the major cause of mortality was injecting the allergen extract to patients with uncontrolled asthma at the time of injection.
AREAS COVERED
This awareness resulted in a significant decrease in fatalities, but not in their abolition. In 2019, an increase in SCIT-related mortality was observed, suggesting to continue the research for still unidentified factors favoring severe reactions, such as the administration of a wrong extract or of allergen doses higher than listed, unintentional intravenous administration, and missed dose reduction after protracted interruption. Moreover, in the context of the improving of the safety, the role played in tolerance-promoting by adjuvants such as CpG oligodeoxynucleotides has to be taken into account, as well as the potential preventive effect performed by the monoclonal anti-IgE antibody omalizumab against the exacerbation of severe reactions during SCIT.
CONCLUSION
The safety of SCIT is good, but the research to improve it further must continue. In particular, the pathophysiological mechanisms related to AIT for inhalants and for Hymenoptera venom should be studied, based on the evident diversity demonstrated by the complete absence of fatal reactions to Hymenoptera venom immunotherapy from its introduction in comparison with the history of serious and fatal offenses examined in this review.
Topics: Humans; Allergens; Desensitization, Immunologic; Hypersensitivity; Asthma; Injections, Subcutaneous
PubMed: 37539607
DOI: 10.23750/abm.v94i4.14239 -
BMC Immunology Jul 2023Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment....
BACKGROUND
Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR.
METHODS
The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment.
RESULTS
GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1.
CONCLUSION
Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR.
Topics: Humans; Rhinitis, Allergic; Transcription Factors; MicroRNAs; Allergens; Immunotherapy; Phosphatidylinositol 3-Kinases
PubMed: 37430199
DOI: 10.1186/s12865-023-00556-1 -
EBioMedicine Jul 2023One of the important adverse impacts of climate change on human health is increases in allergic respiratory diseases such as allergic rhinitis and asthma. This impact is... (Review)
Review
One of the important adverse impacts of climate change on human health is increases in allergic respiratory diseases such as allergic rhinitis and asthma. This impact is via the effects of increases in atmospheric carbon dioxide concentration and air temperature on sources of airborne allergens such as pollen and fungal spores. This review describes these effects and then explores three translational mitigation approaches that may lead to improved health outcomes, with recent examples and developments highlighted. Impacts have already been observed on the seasonality, production and atmospheric concentration, allergenicity, and geographic distribution of airborne allergens, and these are projected to continue into the future. A technological revolution is underway that has the potential to advance patient management by better avoiding associated increased exposures, including automated real-time airborne allergen monitoring, airborne allergen forecasting and modelling, and smartphone apps for mitigating the health impacts of airborne allergens.
Topics: Humans; Climate Change; Allergens; Pollen; Asthma
PubMed: 36805358
DOI: 10.1016/j.ebiom.2023.104478 -
Nutrients Sep 2023Food allergy is a common condition that affects millions of people worldwide. It is caused by an abnormal immune response to harmless food antigens, which is influenced... (Review)
Review
Food allergy is a common condition that affects millions of people worldwide. It is caused by an abnormal immune response to harmless food antigens, which is influenced by genetics and environmental factors. Modulating the gut microbiota and immune system with probiotics or genetically modified probiotics confers health benefits to the host and offers a novel strategy for preventing and treating food allergy. This systematic review aims to summarize the current proof of the role of probiotics in food allergy and propose a promising future research direction of using probiotics as a possible strategy of treatment for food allergy.
Topics: Humans; Food Hypersensitivity; Immune System; Gastrointestinal Microbiome; Allergens; Probiotics
PubMed: 37836443
DOI: 10.3390/nu15194159 -
Communications Biology Jul 2023The current report describes a stepwise mechanistic pathway of NLRP3/caspase1/IL-18-regulated immune responses operational in eosinophilic esophagitis (EoE). We show...
The current report describes a stepwise mechanistic pathway of NLRP3/caspase1/IL-18-regulated immune responses operational in eosinophilic esophagitis (EoE). We show that esophageal epithelial cells and macrophage-derived NLRP3 regulated IL-18 initiate the disease and induced IL-5 facilitates eosinophil growth and survival. We also found that A. fumigatus-exposed IL-18 mice or IL-18-neutralized mice are protected from EoE induction. Most importantly, we present that intravascular rIL-18 delivery to ΔdblGATA mice and CD2-IL-5 mice show the development of EoE characteristics feature like degranulated and intraepithelial eosinophils, basal cell hyperplasia, remodeling and fibrosis. Similarly, we show an induced NLRP3-caspase1-regulated IL-18 pathway is also operational in human EoE. Lastly, we present the evidence that inhibitors of NLRP3 and caspase-1 (MCC950, BHB, and VX-765) protect A. fumigatus- and corn-extract-induced EoE pathogenesis. In conclusion, the current study provides a new understanding by implicating NLRP3/caspase1-regulated IL-18 pathway in EoE pathogenesis. The study has the clinical significance and novel therapeutic strategy, which depletes only IL-18-responsive pathogenic eosinophils, not naïve IL-5-generated eosinophils critical for maintaining innate immunity.
Topics: Humans; Mice; Animals; Eosinophilic Esophagitis; Allergens; NLR Family, Pyrin Domain-Containing 3 Protein; Interleukin-5; Interleukin-18
PubMed: 37524769
DOI: 10.1038/s42003-023-05130-4 -
The Journal of Allergy and Clinical... Dec 2023Atopic diseases are characterized by type 2 inflammation, with high levels of allergen-specific T2 cell immune responses and elevated production of IgE. These common... (Review)
Review
Atopic diseases are characterized by type 2 inflammation, with high levels of allergen-specific T2 cell immune responses and elevated production of IgE. These common disorders have increased in incidence around the world, which is partly explained by detrimental disturbances to the early-life intestinal microbiome. Although most studies have focused exclusively on bacterial members of the microbiome, intestinal fungi have started to be recognized for their impact on host immune development and atopy pathogenesis. From this perspective, we review recent findings demonstrating the strong interactions between members of the mycobiome and the host immune system early in life, leading to immune tolerance during eubiosis or inducing sensitization and overt T2 cell responses during dysbiosis. Current evidence places intestinal fungi as central players in the development of allergic diseases and potential targets for atopy prevention and treatments.
Topics: Humans; Mycobiome; Hypersensitivity; Hypersensitivity, Immediate; Allergens; Inflammation; Fungi
PubMed: 37865199
DOI: 10.1016/j.jaci.2023.10.006 -
Frontiers in Immunology 2023Since the late 1970s, there has been an alarming increase in the incidence of asthma and its morbidity and mortality. Acute obstruction and inflammation of allergic... (Review)
Review
Since the late 1970s, there has been an alarming increase in the incidence of asthma and its morbidity and mortality. Acute obstruction and inflammation of allergic asthmatic airways are frequently caused by inhalation of exogenous substances such as allergens cross-linking IgE receptors expressed on the surface of the human lung mast cells (HLMC). The degree of constriction of human airways produced by identical amounts of inhaled allergens may vary from day to day and even hour to hour. Endogenous factors in the human mast cell (HMC)'s microenvironment during allergen exposure may markedly modulate the degranulation response. An increase in allergic responsiveness may significantly enhance bronchoconstriction and breathlessness. This review focuses on the role that the ubiquitous endogenous purine nucleotide, extracellular adenosine 5'-triphosphate (ATP), which is a component of the damage-associated molecular patterns, plays in mast cells' physiology. ATP activates P2 purinergic cell-surface receptors (P2R) to trigger signaling cascades resulting in heightened inflammatory responses. ATP is the most potent enhancer of IgE-mediated HLMC degranulation described to date. Current knowledge of ATP as it relates to targeted receptor(s) on HMC along with most recent studies exploring HMC post-receptor activation pathways are discussed. In addition, the reviewed studies may explain why brief, minimal exposures to allergens (e.g., dust, cat, mouse, and grass) can unpredictably lead to intense clinical reactions. Furthermore, potential therapeutic approaches targeting ATP-related enhancement of allergic reactions are presented.
Topics: Humans; Animals; Mice; Mast Cells; Signal Transduction; Adenosine Triphosphate; Asthma; Lung; Hypersensitivity; Allergens; Receptors, Purinergic P2
PubMed: 37868982
DOI: 10.3389/fimmu.2023.1216580