Allergy最新文献

{"title":"Hypoxia‐reduced YAP phosphorylation enhances expression of Mucin5AC in nasal epithelial cells of chronic rhinosinusitis with nasal polyps","authors":"Bing Zhong, Jing Liu, Hsiao Hui Ong, Jintao Du, Feng Liu, Yafeng Liu, Luo Ba, Silu Sun, De Yun Wang","doi":"10.1111/all.16394","DOIUrl":"https://doi.org/10.1111/all.16394","url":null,"abstract":"BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is an upper respiratory disease characterized by persistent inflammation of the nasal mucosa. However, the mechanism of abnormal Mucin5AC expression by CRSwNP epithelial cells is not fully understood.ObjectiveWe investigated the potential role of yes‐associated protein (YAP) underlying the mechanism of excessive epithelial Mucin5AC expression in CRSwNP in a hypoxic model.MethodsTissue biopsies of CRSwNP (<jats:italic>n</jats:italic> = 60), chronic rhinosinusitis without nasal polyps (CRSsNP) (<jats:italic>n</jats:italic> = 9) and healthy controls (<jats:italic>n</jats:italic> = 30) were investigated together with a well‐established hypoxic model of primary human nasal epithelial cells (hNECs). The expression levels of hypoxia inducible factor (HIF)‐1α and YAP, and the effect of the signaling axis on mucus secretion in hNECs were analyzed.ResultsWe observed a significant elevated expression levels of YAP in patients with CRSwNP and CRSsNP compared to controls. In addition, HIF‐1α expression of CRSwNP was higher than that of control group. Under hypoxic conditions, HIF‐1α was found to regulate the upregulation of YAP in hNECs. Further investigations revealed that HIF‐1α facilitated the activation and nuclear localization of active‐YAP by reducing the phosphorylation of YAP. This mechanism appeared to be linked to HIF‐1α‐mediated inhibition of LATS 1 phosphorylation and subsequent YAP degradation. HIF‐1α was shown to promote the expression of P63 and the levels of Mucin5AC in hNECs by enhancing YAP activation.ConclusionOur findings indicated that hypoxia enhances YAP activation by decreasing p‐LATS 1 and YAP phosphorylation. This has the potential to impact on the proliferation of basal cells and the differentiation of goblet cells in CRSwNP, ultimately leading to a pathological condition characterized by excessive Mucin5AC expression.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"216 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feedback regulation of VISTA and Treg by TNF‐α controls T cell responses in drug allergy","authors":"Lele Sun, Qing Zhao, Suiting Ao, Tingting Liu, Zhenzhen Wang, Jiabao You, Zihao Mi, Yonghu Sun, Xiaotong Xue, Monday O. Ogese, Joshua Gardner, Xiaoli Meng, Dean J. Naisbitt, Hong Liu, Furen Zhang","doi":"10.1111/all.16393","DOIUrl":"https://doi.org/10.1111/all.16393","url":null,"abstract":"BackgroundSevere cutaneous adverse reactions (SCARs) mediated by cytotoxic T lymphocytes are a series of life‐threatening conditions with a mortality of 4%–20%. The clinical application of tumor necrosis factor‐alpha (TNF‐α) antagonist improves the outcome of some SCARs patients; however, this is complicated by the elusive and varied immunopathogenesis.AimTo investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab.MethodsTo clarify the precise process and optimize the therapy regimen of SCARs, we performed single‐cell sequencing, in vitro functional and clinical analysis of patients with SCARs.ResultsWe observed that TNF‐α breaks drug‐specific T‐cell tolerance by inhibiting the expression of V‐type immunoglobulin domain‐containing suppressor of T‐cell activation (VISTA). Furthermore, TNF‐α generated a positive feedback loop in the early phase of drug‐specific T‐cell activation, whereby B cells acted reciprocally on the corresponding T cells to reinforce TNF‐α cytokine expression. In contrast, this pathway of TNF‐α‐VISTA signaling did not operate in memory effector T cells. Drug‐specific memory effector T‐cell responses were inhibited by increasing Treg cell expression in a negative feedback loop, with TNF‐α antagonists preventing the inhibitory effect. These observations align with the clinical analysis that early but not late intervention with TNF‐α antagonists significantly improved outcomes in SCARs patients.ConclusionOur findings defining feedback regulation of VISTA and Treg cells by TNF‐α in different stages of the drug‐specific T‐cell response and, indicate that a Treg agonists, instead of TNF‐α antagonists, could be used for treatment of patients with progressive SCARs.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"1 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive Mediator Profile of Mepolizumab‐Treated Eosinophilic Granulomatosis With Polyangiitis","authors":"Yosuke Kamide, Kyuto Sonehara, Kiyoshi Sekiya, Shigeharu Ueki, Yuto Nakamura, Yukinori Okada, Masami Taniguchi","doi":"10.1111/all.16395","DOIUrl":"https://doi.org/10.1111/all.16395","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"70 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Gestational Supplementation With 2′‐Fucosyllactose Is an Effective Strategy to Prevent Food Allergy","authors":"A. Rousseaux, B. Misme‐Aucouturier, M. Le Romancer, R. Villette, M. Larsen, M. De Carvalho, G. Bouchaud, E. Perrin, S. Barbarot, C. Brosseau, M. Bodinier","doi":"10.1111/all.16396","DOIUrl":"https://doi.org/10.1111/all.16396","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"36 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologics and airway remodeling in asthma: early, late, and potential preventive effects","authors":"G. Varricchi, R. Poto, M. Lommatzsch, G. Brusselle, F. Braido, J. C. Virchow, G. W. Canonica","doi":"10.1111/all.16382","DOIUrl":"https://doi.org/10.1111/all.16382","url":null,"abstract":"Although airway remodeling in severe and/or fatal asthma is stil considered irreversible, its individual components as a cause of clinical symptoms and/or lung function changes remain largely unknown. While inhaled glucocorticoids have not consistently been shown to affect airway remodeling, biologics targeting specific pathways of airway inflammation have been shown to improve lung function, mucus plugging, and airway structural changes that can exceed those seen with glucocorticoids. This superiority of biologic treatment, which cannot be solely explained by insufficient doses or limited durations of glucocorticoid therapies, needs to be further explored. For this field of research, we propose a novel classification of the potential effects of biologics on airway remodeling into three temporal effects: <jats:italic>early effects</jats:italic> (days to weeks, primarily modulating inflammatory processes), <jats:italic>late effects</jats:italic> (months to years, predominantly affecting structural changes), and potential <jats:italic>preventive effects</jats:italic> (outcomes of early treatment with biologics). For the identification of potential <jats:italic>preventive effects</jats:italic> of biologics, we call for studies exploring the impact of early biological treatment on airway remodeling in patients with moderate‐to‐severe asthma, which should be accompanied by a long‐term evaluation of clinical parameters, biomarkers, treatment burden, and socioeconomic implications.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"9 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short‐course subcutaneous treatment with birch pollen allergoids greatly improves symptom and medication scores in birch allergy","authors":"Ralph Mösges, Esther Raskopf, Ludger Klimek, Oliver Pfaar, Stefan Zielen, Elena Xenofontos, Lea Decker, Christian Neuhof, Anna Rybachuk, Cengizhan Acikel, Hacer Sahin, Silke Allekotte, Sandra del Pozo Collado, José Luis Subiza, Miguel Casanovas, Mandy Cuevas","doi":"10.1111/all.16387","DOIUrl":"https://doi.org/10.1111/all.16387","url":null,"abstract":"BackgroundSubcutaneous immunotherapy has emerged as an effective option for treating allergic diseases. Here, we assessed the clinical impact of the mannan‐conjugated birch pollen polymerized allergoid T502 in birch pollen‐induced allergic rhinoconjunctivitis.MethodsIn this prospective, randomized, double‐blind placebo‐controlled phase III trial, 298 birch pollen–allergic adult patients were treated across 28 trial sites in Germany. Patients received either placebo or 23,000 mTU T502 subcutaneously over five pre‐seasonal visits. Efficacy was assessed by comparing the combined symptom and medication score (CSMS) between placebo and T502 during the peak birch pollen season 2022. Safety, tolerability and immunologic effects were also analyzed.ResultsDuring the peak birch pollen season, the median CSMS of the T502 group was reduced by 33% (<jats:italic>p</jats:italic> = 0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.4% (<jats:italic>p</jats:italic> &lt; 0.001) and 56.3% (<jats:italic>p</jats:italic> = 0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.5% (<jats:italic>p</jats:italic> &lt; 0.0001). Production of <jats:italic>Bet v 1</jats:italic> sIgG4 and <jats:italic>Bet v 1</jats:italic> sIgG increased up to 6.2‐fold and 3‐fold respectively in the T502 group (<jats:italic>p</jats:italic> &lt; 0.0001). The sIgE/sIgG4 ratio was strongly reduced in the T502 group at V7 (−62.9%, <jats:italic>p</jats:italic> &lt; 0.0001).No fatalities nor serious adverse events were reported. In total, 16 systemic allergic reactions occurred (Grade I/II).ConclusionsTreatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"156 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced benefit from house dust mite immunotherapy in subjects with low serum levels of LILRA5 or CCL25","authors":"Véronique Bordas‐Le Floch, Anja Heider, Duygu Yazici, Sonia Luce, Cezmi Akdis, Laurent Mascarell","doi":"10.1111/all.16386","DOIUrl":"https://doi.org/10.1111/all.16386","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"127 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections","authors":"Marua Abu Risha,&nbsp;Karosham D. Reddy,&nbsp;Sai Sneha Priya Nemani,&nbsp;Constanze Jakwerth,&nbsp;Carsten Schmidt-Weber,&nbsp;Thomas Bahmer,&nbsp;Gesine Hansen,&nbsp;Erika von Mutius,&nbsp;Klaus F. Rabe,&nbsp;Anna-Maria Dittrich,&nbsp;Ruth Grychtol,&nbsp;Nicole Maison,&nbsp;Bianca Schaub,&nbsp;Matthias V. Kopp,&nbsp;Folke Brinkmann,&nbsp;Silke Meiners,&nbsp;Uta Jappe,&nbsp;Markus Weckmann,&nbsp;the ALLIANCE Study Group as part of the German Centre for Lung Research (DZL)","doi":"10.1111/all.16388","DOIUrl":"10.1111/all.16388","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Humans are subjected to various environmental stressors (bacteria, viruses, pollution) throughout life. As such, an inherent relationship exists between the effect of these exposures with age. The impact of these environmental stressors can manifest through DNA methylation (DNAm). However, whether these epigenetic effects selectively target genes, pathways, and biological regulatory mechanisms remains unclear. Due to the frequency of human rhinovirus (HRV) infections throughout life (particularly in early development), we propose the use of HRV under controlled conditions can model the effect of multiple exposures to environmental stressors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated a prediction model by combining transcriptome and DNAm datasets from human epithelial cells after repeated HRV infections. We applied a novel experimental statistical design and method to systematically explore the multifaceted experimental space (number of infections, multiplicity of infections and duration). Our model included 35 samples, each characterized by the three parameters defining their infection status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Trainable genes were defined by a consistent linear directionality in DNAm and gene expression changes with successive infections. We identified 77 trainable genes which could be further explored in future studies. The identified methylation sites were tracked within a pediatric cohort to determine the relative changes in candidate-trained sites with disease status and age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Repeated viral infections induce an immune training response in bronchial epithelial cells. Training-sensitive DNAm sites indicate alternate divergent associations in asthma compared to healthy individuals. Our novel model presents a robust tool for identifying trainable genes, providing a foundation for future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 12","pages":"3385-3400"},"PeriodicalIF":12.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut permeability and its correlation with patient's traits and blood inflammatory markers in severe asthma: Real-world assessment from the Korean severe asthma registry-2 (KoSAR-2)","authors":"Doo Young Choi,&nbsp;A-Sol Kim,&nbsp;So-Young Park,&nbsp;Joo-Hee Kim,&nbsp;Jin An,&nbsp;Jae-Woo Kwon,&nbsp;Sujeong Kim,&nbsp;Byung Keun Kim,&nbsp;Young-Hee Nam,&nbsp;Min-Suk Yang,&nbsp;Hye-Kyung Park,&nbsp;Hwa Young Lee,&nbsp;Hae-Sim Park,&nbsp;Seung-Eun Lee,&nbsp;Taehoon Lee,&nbsp;Min-Hye Kim,&nbsp;Chan Sun Park,&nbsp;Da Woon Sim,&nbsp;Woo-Jung Song,&nbsp;Sang-Heon Kim,&nbsp;Han-Ki Park,&nbsp;the KoSAR investigators","doi":"10.1111/all.16392","DOIUrl":"10.1111/all.16392","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 12","pages":"3512-3516"},"PeriodicalIF":12.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA hypomethylation of Th17 cells by ambient particulate pollutants enhances neutrophil recruitment in murine models of allergic airway inflammation","authors":"Bin Li, Yuan Zhang, Nannan Huang, Jing Wang, Xianan Zhang, Qingtao Meng, Jiajia Wang, Chengshuo Wang, Xiaobo Li, Rui Chen, Luo Zhang","doi":"10.1111/all.16389","DOIUrl":"https://doi.org/10.1111/all.16389","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"28 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}