{"title":"Microenvironment-Driven Mast Cell Plasticity: Insights From Cytokine-Activated Gene Signatures in Skin and Respiratory Diseases.","authors":"Chiara Tontini,Rajia Bahri,Andrew Higham,Dave Singh,Angela Simpson,Silvia Bulfone-Paus","doi":"10.1111/all.70052","DOIUrl":"https://doi.org/10.1111/all.70052","url":null,"abstract":"Mast cells (MCs) rapidly adapt to the microenvironment due to the plethora of cytokine receptors expressed. Understanding microenvironment-primed immune responses is essential to elucidate the phenotypic/functional changes MCs undergo, and thus understand their contribution to diseases and predict the most effective therapeutic strategies. We exposed primary human MCs to cytokines mimicking a T1/pro-inflammatory (IFNγ), T2/allergic (IL-4 + IL-13), alarmin-rich (IL-33) and pro-fibrotic/pro-tolerogenic (TGFβ) microenvironment. We investigated MC surface receptor expression, activation, cytokine, histamine, and prostaglandin D2 release, and performed transcriptomics to define shared and unique genetic features. Using machine learning, we extracted minimal cytokine-activated signatures and performed gene set variation analysis (GSVA), single-cell clustering, and pseudotime analyses on tissue MCs from skin and respiratory diseases. MCs exposed in vitro to IFNγ acquire an antigen-presenting phenotype (HLA-DR+), increase IgE-mediated responses and histamine release, while TGFβ inhibits activation and boosts integrin αvβ3 expression. IL-33 primarily drives cytokine (GM-CSF, IL-5, IL-10, IL-13) and chemokine production (IL-8, MCP-1, MIP-1α) and facilitates mixed IgG-IgE responses. Among uniquely expressed genes, 245 were highly informative to discriminate cytokine-primed MCs. GSVA revealed MC IL-4 + IL-13 signatures enriched in atopic dermatitis and psoriasis, IFNγ in COVID-19 infection and cystic fibrosis, IL-33 in COVID-19 and chronic obstructive pulmonary disease (COPD) and TGFβ in pulmonary fibrosis (PF) and chronic rhinosinusitis. Furthermore, we detected positive IL-33/TGFβ priming in eosinophil-high COPD. Minimal cytokine-activated signatures identified disease-cytokine-specific MC clusters and pseudotime trajectories, suggesting involvement of MCs in fibrosis (COPD/PF), T1/alarmin-driven inflammation (COVID-19) and mixed T1/T2 inflammatory responses (AD/psoriasis). In conclusion, in cytokine-driven settings, MCs are phenotypically and functionally diverse. Thus, unique MC signatures will help to identify cytokine-primed MCs and predict the efficacy of anti-cytokine treatment in MC-driven diseases.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"24 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025417","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}
AllergyPub Date : 2025-09-09DOI: 10.1111/all.70035
{"title":"Correction to \"The Impact of Rhinovirus, Syncytial Respiratory Virus and Helminth Infection on the Risk of New-Onset Asthma and Other Allergic Conditions-A Systematic Review for the EAACI Guidelines on Environmental Science for Allergic Diseases and Asthma\".","authors":"","doi":"10.1111/all.70035","DOIUrl":"https://doi.org/10.1111/all.70035","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022509","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}
AllergyPub Date : 2025-09-08DOI: 10.1111/all.16676
Anne Steinberg, Sophie Goebel, Tara Eckert, Meral Sturmfels, Lara Meixner, Stefan Schülke, Katharina Blumchen, Kirsten Beyer, Birgit Ahrens
{"title":"Premastication—Review of an Infant Feeding Practice and Its Potential Impact on Allergy and Microbiome Development","authors":"Anne Steinberg, Sophie Goebel, Tara Eckert, Meral Sturmfels, Lara Meixner, Stefan Schülke, Katharina Blumchen, Kirsten Beyer, Birgit Ahrens","doi":"10.1111/all.16676","DOIUrl":"10.1111/all.16676","url":null,"abstract":"<p>Premastication, or pre-chewing, of food as a feeding practice for infants has been practiced across cultures as an ancient evolutionary method. Whilst literature on the topic remains slim, the majority of existing research has highlighted the potential risks, such as transmission of infections. Although the concerns are valid, potential beneficial aspects have, until now, received less attention. These benefits are hypothesised to include exposure to a healthy, balanced oral microbiome, in combination with the anti-inflammatory properties of saliva and the pre-digestion of food by salivary enzymes. The hypothesis is supported by various studies that have shown the importance of early exposure to microbes for the development of the child's immune system. Moreover, a more varied microbiome earlier on in life is assumed to reduce the development of atopic diseases. Provided that the person chewing and its receiver/the child are healthy, premastication could offer a simple, well-rehearsed method to shape the child's immune system with health-promoting effects particularly in regard to primary allergy prevention. The interactive benefits of transferring an immune-stimulating pre-digested soft food portion containing small amounts of (diverse) food proteins via the oral route could be a valuable contribution to oral tolerance development in the decisive period of microbial-driven immune system maturation. This review aims to evaluate the risks but especially the potential benefits of premastication, by focussing on its possible implications in (food) allergy prevention and oral tolerance development.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":"2726-2737"},"PeriodicalIF":12.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16676","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008707","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}
AllergyPub Date : 2025-09-08DOI: 10.1111/all.70046
Sophie A. Rosser, Melanie Lloyd, Ping Tang, Audrey M. Walsh, Rachel L. Peters, Rushani Wijesuriya, Catherine J. Hornung, Jennifer J. Koplin, Amalia Karahalios, Mimi L. K. Tang
{"title":"Systematic Review and Meta-Analysis of Oral Immunotherapy Effect on Food Allergy-Related Quality of Life","authors":"Sophie A. Rosser, Melanie Lloyd, Ping Tang, Audrey M. Walsh, Rachel L. Peters, Rushani Wijesuriya, Catherine J. Hornung, Jennifer J. Koplin, Amalia Karahalios, Mimi L. K. Tang","doi":"10.1111/all.70046","DOIUrl":"10.1111/all.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Uncertainty exists regarding the health-related quality of life (HRQL) benefits of food allergen oral immunotherapy (OIT). Up-to-date meta-analyses incorporating HRQL data from recent randomised trials are lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Systematic searches of MEDLINE, Embase, CENTRAL and Google Scholar were conducted for food OIT randomised trials (versus any comparator) that measured HRQL with a validated instrument (27 July 2023). Hedges' <i>g</i> standardised mean differences in HRQL between OIT and comparator were analysed by allergen, reporting perspective, and treatment/post-treatment periods, and synthesised using random-effects meta-analysis models when results from multiple trials were available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten trials (nine peanut, one baked milk; <i>N</i> = 1330) were included. No between-group differences were observed in parent-reported child HRQL (<i>g</i> = −0.07, 95% CI: −0.19 to 0.04, 9 trials, <i>N</i> = 1259), self-reported child HRQL (<i>g</i> = −0.23, 95% CI: −0.73 to 0.27, 5 trials, <i>N</i> = 435), or self-reported teenager HRQL (<i>g</i> = 0.00, 95% CI: −0.41 to 0.40, 3 trials, <i>N</i> = 209) during peanut OIT treatment. However, 12 months post-treatment, improved parent-reported child HRQL was observed (<i>g</i> = −0.51, 95% CI: −0.84 to −0.19, 3 comparisons from 2 trials, <i>N</i> = 213). No between-group differences were observed in the baked milk OIT trial in children (<i>g</i> = 0.118, 95% CI: −0.63 to 0.87, <i>N</i> = 26).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HRQL benefits were observed after OIT protocol completion, with limited evidence of benefit during active treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":"2767-2780"},"PeriodicalIF":12.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008791","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}
AllergyPub Date : 2025-09-06DOI: 10.1111/all.70042
George B. Pasikhov, Igor P. Shilovskiy, Aleksandr A. Nikolskii, Kirill V. Yumashev, Mariya M. Kaganova, Danila А. Gurskii, Maya V. Popova, Polina A. Strueva, Nadezda N. Shershakova, Elena V. Kovaleva, Nikolay M. Onatsky, Dmitry A. Kudlay, Rudolf Valenta, Musa R. Khaitov
{"title":"Recombinant Allergy Vaccine‐Induced Transmission of Maternal Allergen‐Specific Neutralizing IgG","authors":"George B. Pasikhov, Igor P. Shilovskiy, Aleksandr A. Nikolskii, Kirill V. Yumashev, Mariya M. Kaganova, Danila А. Gurskii, Maya V. Popova, Polina A. Strueva, Nadezda N. Shershakova, Elena V. Kovaleva, Nikolay M. Onatsky, Dmitry A. Kudlay, Rudolf Valenta, Musa R. Khaitov","doi":"10.1111/all.70042","DOIUrl":"https://doi.org/10.1111/all.70042","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"55 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003160","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":"The Impact of War on Asthma, a Systematic Review and Meta-Analysis: An EAACI Task Force Report.","authors":"João Cavaleiro Rufo,Inês Paciência,Marek Jutel,André Moreira,Isabella Annesi-Maesano,Hille Suojalehto,Magdalena Zemelka-Wiącek,Thulja Trikamjee,Semra Demir,Ibon Eguíluz-Gracia,Daniela Carvalho,Anaïs Backland,Josh Lawson","doi":"10.1111/all.70038","DOIUrl":"https://doi.org/10.1111/all.70038","url":null,"abstract":"Wartime events have been followed by an increase in asthma prevalence, which is believed to result from a combination of environmental hazards and psychological trauma. This systematic review and meta-analysis aimed to investigate this relationship by pooling available data on various wartime exposures, such as occupational, environmental, and psychological factors. MEDLINE, Scopus, and Cochrane databases were searched for articles that measure the effect of war-related exposures on asthma. Risk of bias was assessed using the Effective Public Health Practice Project tool. The retrieved effects were then used to fit meta-analytical models. A total of 48 studies, corresponding to 90 effect measures, were included. War-related post-traumatic stress disorder showed the strongest association with asthma outcomes (OR [95% CI] = 2.25 [1.04, 4.89]), followed by experiencing at least one life-threatening event (1.96 [1.18, 3.26]) and depression (1.56 [1.02, 2.37]). Although environmental exposures were also associated with an increased asthma risk in subgroup analysis (1.64 [1.32, 2.04]), this effect was mitigated when psychological variables were included in the models. The study's results show that wartime events and conflicts may increase asthma prevalence and outcomes associated with asthma. The management of asthma symptoms, lung function, and mental health seems fundamental in individuals who have experienced psychological trauma in war zones. Trial Registration: PROSPERO registration number: CRD42023444101.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"62 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962651","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}