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Nature Aug 2023In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour. The scope and mechanisms of behavioural modifications by...
In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour. The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus and central amygdala. Allergen avoidance requires immunoglobulin E (IgE) antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote avoidance requires cysteinyl leukotrienes and growth and differentiation factor 15. Finally, a comparison of C57BL/6 and BALB/c mouse strains revealed a strong effect of the genetic background on the avoidance behaviour. These findings thus point to antigen-specific behavioural modifications that probably evolved to promote niche selection to avoid unfavourable environments.
Topics: Animals; Mice; Allergens; Avoidance Learning; Central Amygdaloid Nucleus; Disease Models, Animal; Food Hypersensitivity; Immunoglobulin E; Intestines; Mast Cells; Mice, Inbred BALB C; Mice, Inbred C57BL; Parabrachial Nucleus; Solitary Nucleus
PubMed: 37437602
DOI: 10.1038/s41586-023-06362-4 -
Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis.Clinical Gastroenterology and... Jul 2023Dietary therapy for short- and long-term management of eosinophilic esophagitis is an effective yet poorly understood and underutilized treatment strategy. Despite... (Review)
Review
Dietary therapy for short- and long-term management of eosinophilic esophagitis is an effective yet poorly understood and underutilized treatment strategy. Despite several prospective trials demonstrating the efficacy of dietary therapies, successful clinical implementation is hampered by the need for a multidisciplinary approach including dietitian support and provider expertise. The availability of these resources is not readily available to most gastroenterologists. Without standardized guidance on starting or completing the diet for gastrointestinal providers and/or consulting dietitians, provider attitudes toward dietary therapy vary greatly depending on familiarity and knowledge gaps in using diet therapy. This review aims to summarize evidence in support of dietary therapy in eosinophilic esophagitis while providing guidance on initiation and implementation of dietary therapy for providers.
Topics: Eosinophilic Esophagitis; Humans; Elimination Diets; Allergens; Guidelines as Topic
PubMed: 36933603
DOI: 10.1016/j.cgh.2023.03.006 -
Nature Communications Jul 2023Allergic asthma is characterized by goblet cell metaplasia and subsequent mucus hypersecretion that contribute to the morbidity and mortality of this disease. Here, we...
Allergic asthma is characterized by goblet cell metaplasia and subsequent mucus hypersecretion that contribute to the morbidity and mortality of this disease. Here, we explore the potential role and underlying mechanism of protein SUMOylation-mediated goblet cell metaplasia. The components of SUMOylaion machinery are specifically expressed in healthy human bronchial epithelia and robustly upregulated in bronchial epithelia of patients or mouse models with allergic asthma. Intratracheal suppression of SUMOylation by 2-D08 robustly attenuates not only allergen-induced airway inflammation, goblet cell metaplasia, and hyperreactivity, but IL-13-induced goblet cell metaplasia. Phosphoproteomics and biochemical analyses reveal SUMOylation on K1007 activates ROCK2, a master regulator of goblet cell metaplasia, by facilitating its binding to and activation by RhoA, and an E3 ligase PIAS1 is responsible for SUMOylation on K1007. As a result, knockdown of PIAS1 in bronchial epithelia inactivates ROCK2 to attenuate IL-13-induced goblet cell metaplasia, and bronchial epithelial knock-in of ROCK2(K1007R) consistently inactivates ROCK2 to alleviate not only allergen-induced airway inflammation, goblet cell metaplasia, and hyperreactivity, but IL-13-induced goblet cell metaplasia. Together, SUMOylation-mediated ROCK2 activation is an integral component of Rho/ROCK signaling in regulating the pathological conditions of asthma and thus SUMOylation is an additional target for the therapeutic intervention of this disease.
Topics: Animals; Humans; Mice; Allergens; Asthma; Goblet Cells; Inflammation; Interleukin-13; Metaplasia; Sumoylation; rho-Associated Kinases
PubMed: 37393345
DOI: 10.1038/s41467-023-39600-4 -
Allergology International : Official... Oct 2023Fungal sensitization is highly prevalent in severe asthma. The relationship between fungus and asthma, especially Aspergillus fumigatus, has been the subject of... (Review)
Review
Fungal sensitization is highly prevalent in severe asthma. The relationship between fungus and asthma, especially Aspergillus fumigatus, has been the subject of extensive research. The ubiquitous presence of A. fumigatus, its thermotolerant nature, the respirable size of its conidia, and its ability to produce potent allergens are pivotal in worsening asthma control. Due to the diverse clinical manifestations of fungal asthma and the lack of specific biomarkers, its diagnosis remains intricate. Diagnosing fungal asthma requires carefully assessing the patient's clinical history, immunological tests, and imaging. Depending on the severity, patients with fungal asthma require personalized treatment plans, including inhaled corticosteroids and bronchodilators, and antifungal therapy. This review provides a comprehensive overview of the association between Aspergillus and asthma by reviewing the relevant literature and highlighting key findings. We discuss the diagnosis of various entities included in fungal asthma. We also debate whether newer definitions, including allergic fungal airway disease, offer any additional advantages over the existing ones. Finally, we provide the current treatment options for the individual entities, including A. fumigatus-associated asthma, severe asthma with fungal sensitization, and allergic bronchopulmonary mycoses.
Topics: Humans; Aspergillosis, Allergic Bronchopulmonary; Asthma; Aspergillus fumigatus; Allergens; Respiratory System; Mycoses
PubMed: 37633774
DOI: 10.1016/j.alit.2023.08.004 -
Theranostics 2023Perturbation of macrophage homeostasis is one of the key mechanisms of airway inflammation in asthma. However, the exact mechanisms remain poorly understood. We sought...
Perturbation of macrophage homeostasis is one of the key mechanisms of airway inflammation in asthma. However, the exact mechanisms remain poorly understood. We sought to examine the role of histone deacetylase (HDAC) 10 as an epigenetic regulator that governs macrophage M2 program and promotes airway inflammation in asthma, and to elucidate the underlying mechanisms. Peripheral blood and airway biopsies were obtained from healthy individuals and asthmatic patients. Asthma was induced by exposure to allergen in mice with myeloid-specific deletion of (-) mice. HDAC10 inhibitor Salvianolic acid B (SAB), STAT3 selective agonist Colivelin, and the specific PI3K/Akt activator 1,3-Dicaffeoylquinic acid (DA) were also used in asthmatic mice. For cell studies, THP1 cells, primary mouse bone marrow derived macrophage (BMDMs) were used and related signaling pathways was investigated. HDAC10 expression was highly expressed by macrophages and promoted M2 macrophage activation and airway inflammation in asthmatic patients and mice. - mice were protected from airway inflammation in experimental asthma model. deficiency significantly attenuated STAT3 expression and decreased M2 macrophage polarization following allergen exposure. Mechanistically, HDAC10 directly binds STAT3 for deacetylation in macrophages, by which it promotes STAT3 expression and activates the macrophage M2 program. Importantly, we identified SAB as a HDAC10 inhibitor that had protective effects against airway inflammation in mice. Our results revealed that HDAC10-STAT3 interaction governs macrophage polarization to promote airway inflammation in asthma, implicating HDAC10 as a therapeutic target.
Topics: Mice; Animals; Phosphatidylinositol 3-Kinases; Macrophages; Asthma; Inflammation; Allergens; Macrophage Activation
PubMed: 37441601
DOI: 10.7150/thno.82535 -
The Journal of Allergy and Clinical... Aug 2023Group 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 respiratory inflammation, releasing IL-5 and IL-13 and promoting the pulmonary eosinophilia...
BACKGROUND
Group 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 respiratory inflammation, releasing IL-5 and IL-13 and promoting the pulmonary eosinophilia associated with allergen provocation. Although ILC2s have been shown to promote eosinophil activities, the role of eosinophils in group 2 innate lymphoid cell (ILC2) responses is less well defined.
OBJECTIVE
We sought to investigate the role of eosinophils in activation of ILC2s in models of allergic asthma and in vitro.
METHODS
Inducible eosinophil-deficient mice were exposed to allergic respiratory inflammation models of asthma, such as ovalbumin or house dust mite challenge, or to innate models of type 2 airway inflammation, such as inhalation of IL-33. Eosinophil-specific IL-4/13-deficient mice were used to address the specific roles for eosinophil-derived cytokines. Direct cell interactions between ILC2s and eosinophils were assessed by in vitro culture experiments.
RESULTS
Targeted depletion of eosinophils resulted in significant reductions of total and IL-5 and IL-13 lung ILC2s in all models of respiratory inflammation. This correlated with reductions in IL-13 levels and mucus in the airway. Eosinophil-derived IL-4/13 was necessary for both eosinophil and ILC2 accumulation in lung in allergen models. In vitro, eosinophils released soluble mediators that induced ILC2 proliferation and G protein-coupled receptor-dependent chemotaxis of ILC2s. Coculture of ILC2s and IL-33-activated eosinophils resulted in transcriptome changes in both ILC2s and eosinophils, suggesting potential novel reciprocal interactions.
CONCLUSION
These studies demonstrate that eosinophils play a reciprocal role in ILC2 effector functions as part of both adaptive and innate type 2 pulmonary inflammatory events.
Topics: Mice; Animals; Immunity, Innate; Eosinophils; Interleukin-33; Interleukin-13; Interleukin-5; Interleukin-4; Lymphocytes; Lung; Cytokines; Asthma; Inflammation; Allergens
PubMed: 37028525
DOI: 10.1016/j.jaci.2023.03.023 -
Clinical Gastroenterology and... Aug 2023Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of 4 major dietary treatment regimens in EoE, updating the evidence presented in a meta-analysis from 2014.
METHODS
Electronic databases such as PubMed, Scopus, and Web of Science, and other sources were searched up to September 2022 to identify studies on dietary treatment of EoE. Based on histologic remission criteria, the efficacy of these treatments was pooled and analyzed with respect to the type of dietary regimen: 6-food elimination diet (SFED), 4-food elimination diet (FFED), 1-food elimination diet (OFED), and a targeted elimination diet (TED). Clinical response rates, food sensitization, and efficacies for a pediatric subpopulation were calculated. Influencing variables on efficacies were estimated via meta-regression analyses.
RESULTS
Thirty-four studies with 1762 patients met the inclusion criteria. The overall rate of histologic remission was 53.8% (95% CI, 48.0%-59.6%), and in the individual dietary groups was 61.3% (95% CI, 53.0%-69.3%) for SFED, 49.4% (95% CI, 32.5%-66.3%) for FFED, 51.4% (95% CI, 42.6%-60.1%) for OFED, and 45.7% (95% CI, 32.0%-59.7%) for TED. Dietary regimen and patient age did not significantly affect rates of histologic remission. The overall rate of clinical response was 80.8% (95% CI, 72.3%-88.2%), with response rates of 92.8% (95% CI, 81.2%-99.6%) for SFED, 74.1% (95% CI, 49.8%-92.6%) for FFED, 87.1% (95% CI, 58.4%-99.9%) for OFED, and 69.0% (95% CI, 50.2%85.3%) for TED.
CONCLUSIONS
Dietary therapy is an effective treatment for EoE patients of any age. The current results could support a trend toward less-restrictive dietary regimens as a primary treatment option.
Topics: Child; Humans; Allergens; Diet; Elimination Diets; Eosinophilic Esophagitis; Food; Treatment Outcome
PubMed: 36731591
DOI: 10.1016/j.cgh.2023.01.019 -
Nutrients Jul 2023Shellfish is a leading cause of food allergy and anaphylaxis worldwide. Recent advances in molecular characterization have led to a better understanding of the allergen... (Review)
Review
Shellfish is a leading cause of food allergy and anaphylaxis worldwide. Recent advances in molecular characterization have led to a better understanding of the allergen profile. High sequence homology between shellfish species and between shellfish and house dust mites leads to a high serological cross-reactivity, which does not accurately correlate with clinical cross-reactions. Clinical manifestations are immediate and the predominance of perioral symptoms is a typical feature of shellfish allergy. Diagnosis, as for other food allergies, is based on SPTs and specific IgE, while the gold standard is DBPCFC. Cross-reactivity between shellfish is common and therefore, it is mandatory to avoid all shellfish. New immunotherapeutic strategies based on hypoallergens and other innovative approaches represent the new frontiers for desensitization.
Topics: Humans; Child; Shellfish Hypersensitivity; Immunoglobulin E; Shellfish; Food Hypersensitivity; Seafood; Allergens
PubMed: 37513530
DOI: 10.3390/nu15143112 -
La Tunisie Medicale Mar 2024Several clinical and epidemiological data point to a possible link between smoking exposure and contact dermatitis (CD).
INTRODUCTION
Several clinical and epidemiological data point to a possible link between smoking exposure and contact dermatitis (CD).
AIMS
To identify the clinical and epidemiological differences of CD in smoking and non-smoking subjects, and to determine the influence of smoking on the allergological profile of CD.
METHODS
Retrospective descriptive study who consulted the Department of Occupational Medicine and Occupational Pathology of the Farhat Hached University Hospital of Sousse (Tunisia) during a period of 8 years for exploration of CD and who were tested with the European Standard Battery (ESB).
RESULTS
A total of 767 patients were enrolled during the study period, 40% of whom were smokers. The group of smokers was characterized by a male predominance (p=10-3) and a greater professional seniority compared to non-smokers (p=0.01). Personal history of atopy was predominant in non-smokers (p=0.02). Among the ESB allergens, there was a significant association between smoking and CD due to metals (chromium, cobalt) and conservatives. After binary logistic regression, the variables associated with smoking exposure were male gender (OR=12.12 ; 95% CI=[6.07 - 24.21]; p=10-3), Kathon CG allergy (OR=3.69 ; 95% CI=[1.24 - 10.81]; p=0.018), and right hand involvement (OR= 2.83; 95% CI=[1.29 - 6.17]; p=0.005).
CONCLUSION
Our study revealed an effect of smoking on the clinical and allergological characteristics of CD.
Topics: Humans; Male; Female; Dermatitis, Allergic Contact; Retrospective Studies; Smoking; Allergens; Occupations
PubMed: 38545712
DOI: 10.62438/tunismed.v102i3.4226 -
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