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The Journal of Experimental Medicine Nov 2023CD4+ lung-resident memory T cells (TRM) generated in response to influenza infection confer effective protection against subsequent viral exposures. Whether these cells...
CD4+ lung-resident memory T cells (TRM) generated in response to influenza infection confer effective protection against subsequent viral exposures. Whether these cells can be altered by environmental antigens and cytokines released during heterologous, antigen-independent immune responses is currently unclear. We therefore investigated how influenza-specific CD4+ Th1 TRM in the lung are impacted by a subsequent Th2-inducing respiratory house dust mite (HDM) exposure. Although naïve influenza-specific CD4+ T cells in the lymph nodes do not respond to HDM, influenza-specific CD4+ TRM in the lungs do respond to a subsequent allergen exposure by decreasing expression of the transcription factor T-bet. This functional alteration is associated with decreased IFN-γ production upon restimulation and improved disease outcomes following heterosubtypic influenza challenge. Further investigation revealed that ST2 signaling in CD4+ T cells during allergic challenge is necessary to induce these changes in lung-resident influenza-specific CD4+ TRM. Thus, heterologous antigen exposure or ST2-signaling can drive persistent changes in CD4+ Th1 TRM populations and impact protection upon reinfection.
Topics: Animals; Humans; Influenza, Human; Interleukin-1 Receptor-Like 1 Protein; CD4-Positive T-Lymphocytes; Th1 Cells; Pyroglyphidae; Allergens
PubMed: 37698553
DOI: 10.1084/jem.20230112 -
European Annals of Allergy and Clinical... Jan 2016The literature on the nature and prevalence of indoor and/or outdoor aeroallergens, atopy and symptoms of rhinitis and asthma in the Middle East region (defined here as... (Review)
Review
The literature on the nature and prevalence of indoor and/or outdoor aeroallergens, atopy and symptoms of rhinitis and asthma in the Middle East region (defined here as Bahrain, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Kingdom of Saudi Arabia - KSA, Syria, United Arab Emirates and Yemen) was reviewed. Although documentation was poor in all countries other than Iran and the KSA, a wide range of "global" and "local" aeroallergens (grass, weed and tree pollens, fungal spores, insect allergens, dander, and house dust mites) has been observed across the region. The prevalence of current self-reported or parent-reported symptoms of rhinitis ranged from 9% to 38%. Researchers have suggested that the high atopy rates and self-reported rhinitis rates are associated with an on-going shift towards a "western" lifestyle.
Topics: Allergens; Animals; Dander; Female; Humans; Hypersensitivity, Immediate; Insecta; Male; Middle East; Pollen; Prevalence; Pyroglyphidae; Rhinitis, Allergic; Spores, Fungal
PubMed: 26808447
DOI: No ID Found -
The Journal of Allergy and Clinical... Mar 2024Patients with severe asthma can present with eosinophilic type 2 (T2), neutrophilic, or mixed inflammation that drives airway remodeling and exacerbations and represents...
BACKGROUND
Patients with severe asthma can present with eosinophilic type 2 (T2), neutrophilic, or mixed inflammation that drives airway remodeling and exacerbations and represents a major treatment challenge. The common β (βc) receptor signals for 3 cytokines, GM-CSF, IL-5, and IL-3, which collectively mediate T2 and neutrophilic inflammation.
OBJECTIVE
To determine the pathogenesis of βc receptor-mediated inflammation and remodeling in severe asthma and to investigate βc antagonism as a therapeutic strategy for mixed granulocytic airway disease.
METHODS
βc gene expression was analyzed in bronchial biopsy specimens from patients with mild-to-moderate and severe asthma. House dust mite extract and Aspergillus fumigatus extract (ASP) models were used to establish asthma-like pathology and airway remodeling in human βc transgenic mice. Lung tissue gene expression was analyzed by RNA sequencing. The mAb CSL311 targeting the shared cytokine binding site of βc was used to block βc signaling.
RESULTS
βc gene expression was increased in patients with severe asthma. CSL311 potently reduced lung neutrophils, eosinophils, and interstitial macrophages and improved airway pathology and lung function in the acute steroid-resistant house dust mite extract model. Chronic intranasal ASP exposure induced airway inflammation and fibrosis and impaired lung function that was inhibited by CSL311. CSL311 normalized the ASP-induced fibrosis-associated extracellular matrix gene expression network and strongly reduced signatures of cellular inflammation in the lung.
CONCLUSIONS
βc cytokines drive steroid-resistant mixed myeloid cell airway inflammation and fibrosis. The anti-βc antibody CSL311 effectively inhibits mixed T2/neutrophilic inflammation and severe asthma-like pathology and reverses fibrosis gene signatures induced by exposure to commonly encountered environmental allergens.
Topics: Mice; Animals; Humans; Receptors, Cytokine; Airway Remodeling; Asthma; Lung; Cytokines; Mice, Transgenic; Inflammation; Allergens; Steroids; Fibrosis; Pyroglyphidae
PubMed: 37931708
DOI: 10.1016/j.jaci.2023.10.021 -
European Annals of Allergy and Clinical... Nov 2017Currently, the management of people diagnosed with shellfish allergy relies on the avoidance of those foods. HDM immunotherapy has been reported to induce both shrimp... (Review)
Review
Currently, the management of people diagnosed with shellfish allergy relies on the avoidance of those foods. HDM immunotherapy has been reported to induce both shrimp allergy in non-allergic patients, and shrimp tolerance in shrimp-allergic patients. This article summarizes therapeutic options other than avoidance diet for shrimp allergic patients available once the diagnostic is established, such as production of hypoallergenic shrimp, use of immunotherapy with modified allergens, probiotics and Chinese herbal formulations.
Topics: Allergens; Animals; Desensitization, Immunologic; Drugs, Chinese Herbal; Epitopes, T-Lymphocyte; Humans; Immunoglobulin E; Penaeidae; Probiotics; Pyroglyphidae; Seafood; Shellfish Hypersensitivity; Sublingual Immunotherapy; Treatment Outcome; Tropomyosin; Vaccination
PubMed: 29249132
DOI: 10.23822/EurAnnACI.1764-1489.16 -
The Journal of Allergy and Clinical... Mar 2017
Topics: Animals; Dermatophagoides pteronyssinus; Epithelial Cells; Hypersensitivity; Inflammation; Pyroglyphidae
PubMed: 27993537
DOI: 10.1016/j.jaci.2016.11.018 -
The Journal of Allergy and Clinical... Feb 2023Alternaria alternata and house dust mite exposure evokes IL-33 secretion from the airway epithelium, which functions as an alarmin to stimulate type 2 immunity....
BACKGROUND
Alternaria alternata and house dust mite exposure evokes IL-33 secretion from the airway epithelium, which functions as an alarmin to stimulate type 2 immunity. Extracellular DNA (eDNA) is also an alarmin that intensifies inflammation in cystic fibrosis, chronic obstructive pulmonary disease, and asthma.
OBJECTIVE
We investigated the mechanisms underlying allergen-evoked DNA mobilization and release from the airway epithelium and determined the role of eDNA in type 2 immunity.
METHODS
Human bronchial epithelial (hBE) cells were used to characterize allergen-induced DNA mobilization and extracellular release using comet assays to measure DNA fragmentation, Qubit double-stranded DNA assays to measure DNA release, and DNA sequencing to determine eDNA composition. Mice were used to investigate the role of eDNA in type 2 immunity.
RESULTS
Alternaria extract rapidly induces mitochondrial and nuclear DNA release from human bronchial epithelial cells, whereas house dust mite extract induces mitochondrial DNA release. Caspase-3 is responsible for nuclear DNA fragmentation and becomes activated after cleavage by furin. Analysis of secreted nuclear DNA showed disproportionally higher amounts of promotor and exon sequences and lower intron and intergenic regions compared to predictions of random DNA fragmentation. In mice, Alternaria-induced type 2 immune responses were blocked by pretreatment with a DNA scavenger. In caspase-3-deficient mice, Alternaria-induced DNA release was suppressed. Furthermore, intranasal administration of mouse genomic DNA with Alternaria amplified secretion of IL-5 and IL-13 into bronchoalveolar lavage fluid while DNA alone had no effect.
CONCLUSION
These findings highlight a novel, allergen-induced mechanism of rapid DNA release that amplifies type 2 immunity in airways.
Topics: Mice; Humans; Animals; Allergens; Caspase 3; Alarmins; Epithelium; Pyroglyphidae; DNA; Lung
PubMed: 36306937
DOI: 10.1016/j.jaci.2022.09.034 -
International Immunopharmacology Dec 2022Epithelial barrier dysfunction is involved in the pathogenesis of asthma. Previous studies show that SUMOylation can regulate epithelial junction molecule localization....
Epithelial barrier dysfunction is involved in the pathogenesis of asthma. Previous studies show that SUMOylation can regulate epithelial junction molecule localization. However, the role of SUMOylation in epithelial barrier dysfunction in asthma remains unclear. This study found that inhibition of SUMOylation attenuates house dust mite (HDM)-induced epithelial barrier dysfunction. The SUMOylation levels of junction molecules were determined by co-immunoprecipitation (CO-IP) and proximity ligation assay (PLA). HDM treatment significantly enhanced SUMOylation levels of β-catenin, while no effect was seen on ZO-1, Occludin, and E-cadherin SUMOylation levels. Inhibition of β-catenin SUMOylation through 2-D08 treatment or SUMOylation modification site mutant (K233A) promoted its membrane localization and repressed Wnt/β-catenin signaling. Further, we identified that CBX4, an E3 ligase, mediated SUMOylation of β-catenin. Knockdown of CBX4 promoted β-catenin membrane localization and improved epithelial barrier function. In vivo analysis showed that AAV6-shCBX4-mediated knockdown of CBX4 attenuated HDM-induced allergic airway inflammation and epithelial barrier dysfunction. The findings showed that inhibiting β-catenin SUMOylation by targeting CBX4 mitigated HDM-induced epithelial barrier dysfunction in asthma.
Topics: Animals; Humans; beta Catenin; Sumoylation; Cell Line; Pyroglyphidae; Asthma; Dermatophagoides pteronyssinus; Ligases; Polycomb-Group Proteins
PubMed: 36306558
DOI: 10.1016/j.intimp.2022.109333 -
Frontiers in Immunology 2023To systematically evaluate the clinical efficacy and safety of sublingual immunotherapy for allergic rhinitis (AR) and provide evidence for clinical treatment. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To systematically evaluate the clinical efficacy and safety of sublingual immunotherapy for allergic rhinitis (AR) and provide evidence for clinical treatment.
METHODS
A literature search was performed on the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Web of Science, Cochrane Library, and Embase database. Data from randomized controlled trials (RCTs) of sublingual immunotherapy for AR were screened and extracted from the establishment of those databases to November 2022. Subsequently, a network meta-analysis was performed using a statistical software R 4.2.
RESULTS
Totally 22 RCTs that met the inclusion and exclusion criteria and screened from 1,164 literature were included. A total of 4,941 AR patients were involved in the 22 trials, as well as five interventions including placebo, pharmacotherapy, subcutaneous immunotherapy_dust mite, sublingual immunotherapy_dust mite, and sublingual immunotherapy_ grass mix plus pollen extract. The results of network meta-analysis showed that, based on symptom scores after different interventions for AR, the most effective treatments for AR were in order as follows: sublingual immunotherapy_dust mite, subcutaneous immunotherapy_dust mite, sublingual immunotherapy_ grass mix plus pollen extract, placebo, and pharmacotherapy. Importantly, sublingual immunotherapy had fewer adverse reactions and higher safety.
CONCLUSION
Sublingual immunotherapy_dust mite for AR has the best efficacy, whereas traditional medicine has the worst. More high-quality studies with a large sample and multiple centers are needed to verify this conclusion in the future, so as to further provide more reliable evidence-based medical evidence for the clinical treatment options of AR patients.
Topics: Animals; Humans; Sublingual Immunotherapy; Network Meta-Analysis; Rhinitis, Allergic; Pyroglyphidae; Plant Extracts
PubMed: 37063866
DOI: 10.3389/fimmu.2023.1144816 -
Frontiers in Immunology 2023Extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers, such as skin and intestine, has been shown to be important in the local regulation of inflammation....
BACKGROUND
Extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers, such as skin and intestine, has been shown to be important in the local regulation of inflammation. However, the role of local GC synthesis in the lung is less well studied. Based on previous studies and the uncontentious efficacy of corticosteroid therapy in asthma patients, we here investigated the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1/)-dependent local GC reactivation in the regulation of allergic airway inflammation.
METHODS
Airway inflammation in Hsd11b1-deficient and C57BL/6 wild type mice was analyzed after injection of lipopolysaccharide (LPS) and anti-CD3 antibody, and in acute and chronic models of airway hypersensitivity induced by house dust mite (HDM) extract. The role of 11β-HSD1 in normal and inflammatory conditions was assessed by high dimensional flow cytometry, histological staining, RT-qPCR analysis, tissue cultures, GC-bioassays and protein detection by ELISA and immunoblotting.
RESULTS
Here we show that lung tissue from Hsd11b1-deficient mice synthesized significantly less GC compared with wild type animals in response to immune cell stimulation. We further observed a drastically aggravated phenotype in Hsd11b1-deficient mice treated with HDM extract compared to wild type animals. Besides eosinophilic infiltration, Hsd11b1-deficient mice exhibited aggravated neutrophilic infiltration caused by a strong Th17-type immune response.
CONCLUSION
We propose an important role of 11β-HSD1 and local GC in regulating Th17-type rather than Th2-type immune responses in HDM-induced airway hypersensitivity in mice by potentially controlling Toll-like receptor 4 (TLR4) signaling and cytokine/chemokine secretion by airway epithelial cells.
Topics: Humans; Animals; Mice; Glucocorticoids; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Mice, Inbred C57BL; Inflammation; Dust Mite Allergy; Allergens; Pyroglyphidae
PubMed: 37936704
DOI: 10.3389/fimmu.2023.1252874 -
Respiratory Medicine 2023Allergen specific immunotherapy (AIT) is the only causal therapeutic option for allergic airway diseases including asthma and allergic rhinitis. AIT has been shown to... (Review)
Review
Allergen specific immunotherapy (AIT) is the only causal therapeutic option for allergic airway diseases including asthma and allergic rhinitis. AIT has been shown to restore the allergen immune tolerance, can modify both the early and late-onset allergen-specific airway hyperreactivity, helps to achieve disease control/remission and prevents new sensitisations. Recent real life data on long-term effectiveness of house dust mite (HDM) AIT in a large group of patients with HDM-driven asthma further underscored its unique therapeutic potential as well as confirmed previous data with pollen AIT. More widespread use of this causal treatment in select patient populations should further move this promising therapeutic field. In this mini-review, we discuss updates on new insights based on real world patient data.
Topics: Animals; Humans; Asthma; Desensitization, Immunologic; Rhinitis, Allergic; Allergens; Pollen; Antigens, Dermatophagoides; Pyroglyphidae; Sublingual Immunotherapy
PubMed: 36702170
DOI: 10.1016/j.rmed.2023.107125