Diego Alvarado,Deena M Maurer,Philip Golden,Thomas Hawthorne,Lawrence J Thomas,Margo Heath-Chiozzi,Tibor Keler,Elizabeth Crowley,Diane Young,Dorothea Terhorst-Molawi,Melba Munoz,Martin Metz
{"title":"On the Kinetics of Human Skin Mast Cell Depletion and Repopulation Following KIT Inhibition.","authors":"Diego Alvarado,Deena M Maurer,Philip Golden,Thomas Hawthorne,Lawrence J Thomas,Margo Heath-Chiozzi,Tibor Keler,Elizabeth Crowley,Diane Young,Dorothea Terhorst-Molawi,Melba Munoz,Martin Metz","doi":"10.1111/all.70129","DOIUrl":"https://doi.org/10.1111/all.70129","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"105 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351532","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}
Aspartame has been widely used as a sweetener in foods and beverages since the 1980s. In this study, we aimed to assess its effects on gut epithelial cell biology, inflammation and the epithelial barrier. We found that aspartame induces cytotoxic effects, disrupts the epithelial barrier and triggers proinflammatory cytokine release in gastrointestinal epithelial cells, organoids and gut-on-a-chip models at concentrations corresponding to daily consumed doses in food products. Cellular cytotoxicity was observed at doses as low as 1.25 mg/mL. RNA sequencing analysis revealed that aspartame significantly alters the transcriptome in gut-on-a-chip models, with upregulation of pathways involved in the unfolded protein response, pro-apoptotic and inflammatory processes and downregulation of those related to DNA repair and replication. Aspartame exposure upregulated proinflammatory genes, particularly in the TNF signalling pathway, and induced multiple chemokine responses. It also activated the NF-κB pathway via oxidative stress, promoting inflammation in NF-κB reporter monocyte cells and leading to gut epithelial cell death. Additionally, aspartame affected genes involved in tight and adherens junctions, disrupting gut epithelial barrier integrity in a dose-dependent manner. It further suppressed key DNA repair and replication genes associated with double-strand break repair, mismatch repair and DNA replication. Overall, our findings indicate that, at commonly consumed levels, aspartame induces cellular stress, inflammation and epithelial barrier damage in gastrointestinal epithelial cells. These results underscore the biological relevance of our study and raise concerns that daily dietary intake of aspartame may pose previously underappreciated risks to gut health.
{"title":"Cellular Stress, Inflammation and Barrier Damage in Gut Epithelial Cells Caused by Aspartame.","authors":"Yagiz Pat,Duygu Yazici,Can Zeyneloglu,Huseyn Babayev,Sena Ardicli,Asuncion Garci-Sanchez,Xiangting Bu,Anja Heider,Oliva Giannelli Viscardi,Lihong Chang,Sheri Simmons,Anthony Almada,Christine Avena,Tye Jensen,Raja Dhir,Ismail Ogulur,Cezmi A Akdis","doi":"10.1111/all.70095","DOIUrl":"https://doi.org/10.1111/all.70095","url":null,"abstract":"Aspartame has been widely used as a sweetener in foods and beverages since the 1980s. In this study, we aimed to assess its effects on gut epithelial cell biology, inflammation and the epithelial barrier. We found that aspartame induces cytotoxic effects, disrupts the epithelial barrier and triggers proinflammatory cytokine release in gastrointestinal epithelial cells, organoids and gut-on-a-chip models at concentrations corresponding to daily consumed doses in food products. Cellular cytotoxicity was observed at doses as low as 1.25 mg/mL. RNA sequencing analysis revealed that aspartame significantly alters the transcriptome in gut-on-a-chip models, with upregulation of pathways involved in the unfolded protein response, pro-apoptotic and inflammatory processes and downregulation of those related to DNA repair and replication. Aspartame exposure upregulated proinflammatory genes, particularly in the TNF signalling pathway, and induced multiple chemokine responses. It also activated the NF-κB pathway via oxidative stress, promoting inflammation in NF-κB reporter monocyte cells and leading to gut epithelial cell death. Additionally, aspartame affected genes involved in tight and adherens junctions, disrupting gut epithelial barrier integrity in a dose-dependent manner. It further suppressed key DNA repair and replication genes associated with double-strand break repair, mismatch repair and DNA replication. Overall, our findings indicate that, at commonly consumed levels, aspartame induces cellular stress, inflammation and epithelial barrier damage in gastrointestinal epithelial cells. These results underscore the biological relevance of our study and raise concerns that daily dietary intake of aspartame may pose previously underappreciated risks to gut health.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"39 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357801","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}
Gesa J Albers,Patricia P Ogger,Christina Michalaki,Helen Stölting,Simone A Walker,Anna Caldwell,John M Halket,Kathryn Duvall,Atia Batool,Lisha Joshi,Helen O'Brien,Cormac McCarthy,Timothy Hinks,Gail M Gauvreau,Paul M O'Byrne,Clare M Lloyd,Adam J Byrne
BACKGROUNDAsthma is a chronic, heterogeneous disease characterised by airway remodelling, inflammation, and mucus production. Airway macrophages' functions are underpinned by changes in cellular metabolism. The TCA cycle-derived metabolite itaconic acid (whose synthesis is mediated by aconitate decarboxylase) is a master regulator of macrophage function; however, its role during inhaled allergen challenge is not clear. The objective of this study was to define the role of itaconate during inhaled allergen challenge.METHODSSputum metabolite levels were measured in participants with mild allergic asthma undergoing allergen inhalation challenge, and in a second cohort, baseline levels in mild, moderate, and severe asthmatics. Airway inflammation, lung function, and bronchoalveolar lavage metabolite levels were assessed in wild-type and aconitate decarboxylase-deficient mice, or in mice treated with inhaled itaconate.RESULTSAllergen inhalation in mild asthmatics led to a significant reduction in sputum itaconate. We found no difference in baseline sputum itaconate levels when comparing healthy controls to mild, moderate, or severe asthmatics. Continuous exposure to aeroallergen in wild type and aconitate decarboxylase-deficient mice showed no change in disease phenotype after 48 h, 1, 3, or 5 weeks of allergen exposure. Treatment of house dust mite-exposed mice with inhaled itaconate reduced airway inflammation.CONCLUSIONLevels of itaconate are altered after allergen challenge in mild asthmatics and in murine models of disease. Itaconate deficiency did not alter house dust mite-induced pathology at any of the timepoints tested; however, inhaled itaconate ameliorated inflammatory responses to inhaled allergen.
{"title":"Protective Role for Itaconate During Inhaled Allergen Challenge.","authors":"Gesa J Albers,Patricia P Ogger,Christina Michalaki,Helen Stölting,Simone A Walker,Anna Caldwell,John M Halket,Kathryn Duvall,Atia Batool,Lisha Joshi,Helen O'Brien,Cormac McCarthy,Timothy Hinks,Gail M Gauvreau,Paul M O'Byrne,Clare M Lloyd,Adam J Byrne","doi":"10.1111/all.70107","DOIUrl":"https://doi.org/10.1111/all.70107","url":null,"abstract":"BACKGROUNDAsthma is a chronic, heterogeneous disease characterised by airway remodelling, inflammation, and mucus production. Airway macrophages' functions are underpinned by changes in cellular metabolism. The TCA cycle-derived metabolite itaconic acid (whose synthesis is mediated by aconitate decarboxylase) is a master regulator of macrophage function; however, its role during inhaled allergen challenge is not clear. The objective of this study was to define the role of itaconate during inhaled allergen challenge.METHODSSputum metabolite levels were measured in participants with mild allergic asthma undergoing allergen inhalation challenge, and in a second cohort, baseline levels in mild, moderate, and severe asthmatics. Airway inflammation, lung function, and bronchoalveolar lavage metabolite levels were assessed in wild-type and aconitate decarboxylase-deficient mice, or in mice treated with inhaled itaconate.RESULTSAllergen inhalation in mild asthmatics led to a significant reduction in sputum itaconate. We found no difference in baseline sputum itaconate levels when comparing healthy controls to mild, moderate, or severe asthmatics. Continuous exposure to aeroallergen in wild type and aconitate decarboxylase-deficient mice showed no change in disease phenotype after 48 h, 1, 3, or 5 weeks of allergen exposure. Treatment of house dust mite-exposed mice with inhaled itaconate reduced airway inflammation.CONCLUSIONLevels of itaconate are altered after allergen challenge in mild asthmatics and in murine models of disease. Itaconate deficiency did not alter house dust mite-induced pathology at any of the timepoints tested; however, inhaled itaconate ameliorated inflammatory responses to inhaled allergen.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"119 8 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357802","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}
Wildfire smoke is a major environmental health threat that has increased in frequency and severity in recent years. A hazardous component of wildfire smoke is particulate matter ≤ 2.5 μm (PM2.5). There is evidence to suggest that exposure to wildfire PM2.5 may increase the risk of developing or exacerbating atopic diseases, such as asthma, allergic rhinitis, and atopic dermatitis. Certain communities may be disproportionately affected due to a lack of access to resources and information about how to protect themselves. This review highlights the negative impacts of wildfire smoke on atopic diseases and effects on specific communities. Further research is needed to better understand factors that contribute to the impact of wildfire smoke and to develop strategies and policy interventions for mitigation.
{"title":"Wildfires and Atopic Diseases: A Review.","authors":"Alex Ha,John R Balmes,Maria L Wei","doi":"10.1111/all.70116","DOIUrl":"https://doi.org/10.1111/all.70116","url":null,"abstract":"Wildfire smoke is a major environmental health threat that has increased in frequency and severity in recent years. A hazardous component of wildfire smoke is particulate matter ≤ 2.5 μm (PM2.5). There is evidence to suggest that exposure to wildfire PM2.5 may increase the risk of developing or exacerbating atopic diseases, such as asthma, allergic rhinitis, and atopic dermatitis. Certain communities may be disproportionately affected due to a lack of access to resources and information about how to protect themselves. This review highlights the negative impacts of wildfire smoke on atopic diseases and effects on specific communities. Further research is needed to better understand factors that contribute to the impact of wildfire smoke and to develop strategies and policy interventions for mitigation.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"108 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339186","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}
Philip H. Li, Vito Sabato, David A. Khan, Michaela Lucas, Juan Meng, Jonny Peter, Jason A. Trubiano, Mohamed H. Shamji, Maria Jose Torres
<p>At the inaugural EAACI Hong Kong Allergy School (August 27–29, 2025), more than 340 participants from 37 countries gathered under the theme “East Meets West.” As one of the main themes, a landmark roundtable united drug allergy experts from Africa, America, Asia, Australasia, and Europe, fostered an unprecedented global exchange and a unified call for international consensus. Two priorities emerged: establishing universal drug “allergy” nomenclature and definitions of “low-risk” penicillin allergy.</p><p>Drug allergy (or “hypersensitivity”) remains a global health concern, but progress has been hindered by the lack of a unified nomenclature. Notably, even the distinction between “allergy” and “hypersensitivity” remains actively debated worldwide. The term “allergy” (derived from the Greek <i>allos</i> [other] and <i>ergon</i> [reaction]) was originally coined as a neutral descriptor for altered immune reactivity to a substance [<span>1</span>]. In this context, “hypersensitivity” was intended to denote a harmful response of such reactivity. However, various disputes and the parallel evolution of definitions for related conditions (e.g., anaphylaxis) over time have contributed to inconsistent interpretations of the terms “allergy” and “hypersensitivity”. Gell and Coombs introduced the four classic types of immune-mediated reactions which became the cornerstone of immunopathology and clinical immunology [<span>2</span>]. In 2001 and 2003, EAACI and the World Allergy Organization, respectively, proposed defining “hypersensitivity” as “objectively reproducible symptoms or signs triggered by a stimulus tolerated by normal individuals” [<span>3, 4</span>]. In this system, “hypersensitivity reactions” refer to adverse responses initiated by specific immunologic mechanisms (as defined by Gell and Coombs' classification), whereas “nonallergic hypersensitivity” describes reactions that occur without evidence of an immunologic basis. More specifically for drug reactions, the International CONsensus (ICON) on drug allergy defines drug hypersensitivity as “adverse effects of pharmaceuticals that clinically resemble allergy,” while the US Joint Task Force Drug Allergy Practice Parameters acknowledges variable usage in the literature and treats the terms “allergy” and “hypersensitivity” as interchangeable [<span>5, 6</span>]. Figure 1 illustrates various examples of how drug “allergy” versus “hypersensitivity” may currently be defined, highlighting discrepancies in nomenclature.</p><p>However, several considerations complicate the approach to drug allergy/hypersensitivity. Reactions traditionally labeled as “immune-mediated” and those termed “nonimmune mediated” often involve overlapping adaptive and other inflammatory pathways, challenging historical distinctions. Clinical phenotypes frequently do not correlate with underlying mechanisms: a single drug may trigger reactions via haptenization, direct receptor activation (e.g., MRGPRX2 or HLA/TCR-p-i), or enz
{"title":"Unifying Global Drug Allergy: Clarifying Concepts and Defining Low-Risk Penicillin Allergy","authors":"Philip H. Li, Vito Sabato, David A. Khan, Michaela Lucas, Juan Meng, Jonny Peter, Jason A. Trubiano, Mohamed H. Shamji, Maria Jose Torres","doi":"10.1111/all.70125","DOIUrl":"10.1111/all.70125","url":null,"abstract":"<p>At the inaugural EAACI Hong Kong Allergy School (August 27–29, 2025), more than 340 participants from 37 countries gathered under the theme “East Meets West.” As one of the main themes, a landmark roundtable united drug allergy experts from Africa, America, Asia, Australasia, and Europe, fostered an unprecedented global exchange and a unified call for international consensus. Two priorities emerged: establishing universal drug “allergy” nomenclature and definitions of “low-risk” penicillin allergy.</p><p>Drug allergy (or “hypersensitivity”) remains a global health concern, but progress has been hindered by the lack of a unified nomenclature. Notably, even the distinction between “allergy” and “hypersensitivity” remains actively debated worldwide. The term “allergy” (derived from the Greek <i>allos</i> [other] and <i>ergon</i> [reaction]) was originally coined as a neutral descriptor for altered immune reactivity to a substance [<span>1</span>]. In this context, “hypersensitivity” was intended to denote a harmful response of such reactivity. However, various disputes and the parallel evolution of definitions for related conditions (e.g., anaphylaxis) over time have contributed to inconsistent interpretations of the terms “allergy” and “hypersensitivity”. Gell and Coombs introduced the four classic types of immune-mediated reactions which became the cornerstone of immunopathology and clinical immunology [<span>2</span>]. In 2001 and 2003, EAACI and the World Allergy Organization, respectively, proposed defining “hypersensitivity” as “objectively reproducible symptoms or signs triggered by a stimulus tolerated by normal individuals” [<span>3, 4</span>]. In this system, “hypersensitivity reactions” refer to adverse responses initiated by specific immunologic mechanisms (as defined by Gell and Coombs' classification), whereas “nonallergic hypersensitivity” describes reactions that occur without evidence of an immunologic basis. More specifically for drug reactions, the International CONsensus (ICON) on drug allergy defines drug hypersensitivity as “adverse effects of pharmaceuticals that clinically resemble allergy,” while the US Joint Task Force Drug Allergy Practice Parameters acknowledges variable usage in the literature and treats the terms “allergy” and “hypersensitivity” as interchangeable [<span>5, 6</span>]. Figure 1 illustrates various examples of how drug “allergy” versus “hypersensitivity” may currently be defined, highlighting discrepancies in nomenclature.</p><p>However, several considerations complicate the approach to drug allergy/hypersensitivity. Reactions traditionally labeled as “immune-mediated” and those termed “nonimmune mediated” often involve overlapping adaptive and other inflammatory pathways, challenging historical distinctions. Clinical phenotypes frequently do not correlate with underlying mechanisms: a single drug may trigger reactions via haptenization, direct receptor activation (e.g., MRGPRX2 or HLA/TCR-p-i), or enz","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 11","pages":"2949-2952"},"PeriodicalIF":12.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338725","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}
BACKGROUNDClub cells, originating from basal cells, can differentiate into ciliated or goblet cells in the lower respiratory tract, but their role in nasal epithelium during chronic rhinosinusitis with nasal polyps (CRSwNP) is not well understood. We aim to investigate the role of club cells in CRSwNP and their biological mechanism in an IL-13-induced inflammation model of human nasal epithelial cells (HNECs).METHODSCRSwNP was classified into four endotypes (N-E-, N+E-, N-E+, and N+E+) based on neutrophil and eosinophil infiltration. The expression of basal (TP63+), club (SCGB1A1+), ciliated (βIV-tubulin+), and goblet cells (MUC5AC+) was assessed in healthy controls (n = 23) and CRSwNP (n = 73) using RT-qPCR, western blot (WB), and immunofluorescence. The effects of IL-13, Dupilumab, and STAT6 inhibitor (AS1517499) on cell differentiation were investigated in HNECs (n = 9) through RT-qPCR, WB, and flow cytometry (FCM).RESULTSClub and ciliated cells significantly decreased in four endotypes of CRSwNP (all p < 0.001), while basal and goblet cells increased in neutrophilic and eosinophilic CRSwNP, respectively (all p < 0.05). In vitro, IL-13-induced significant cilia loss and MUC5AC secretion compared to IFN-γ and IL-17A (all p < 0.05), and FCM revealed a shift from SCGB1A1+βIV-tubulin+ to SCGB1A1+MUC5AC+ cells by IL-13-treated (all p < 0.05). Furthermore, Dupilumab mitigated IL-13-induced changes more effectively than AS1517499 (all p < 0.05).CONCLUSIONSClub cells are crucial in nasal epithelial repair, which is notably compromised in CRSwNP. This impairment is highlighted in an IL-13-induced inflammation model of nasal epithelium and further underscored by the therapeutic effect of Dupilumab in restoring epithelial repair mechanisms.
俱乐部细胞起源于基底细胞，可以在下呼吸道分化为纤毛细胞或杯状细胞，但它们在慢性鼻窦炎伴鼻息肉（CRSwNP）中在鼻上皮中的作用尚不清楚。我们的目的是在il -13诱导的人鼻上皮细胞（HNECs）炎症模型中研究俱乐部细胞在CRSwNP中的作用及其生物学机制。方法根据中性粒细胞和嗜酸性粒细胞的浸润情况，将scrswnp分为N-E-型、N+E-型、N-E+型和N+E+型。采用RT-qPCR、western blot （WB）和免疫荧光技术检测健康对照（n = 23）和CRSwNP （n = 73）中基底细胞（TP63+）、俱乐部细胞（SCGB1A1+）、纤毛细胞（β iv -微管蛋白+）和杯状细胞（MUC5AC+）的表达。通过RT-qPCR、WB和流式细胞术（FCM）研究IL-13、Dupilumab和STAT6抑制剂（AS1517499）对HNECs （n = 9）细胞分化的影响。结果4种内型CRSwNP中俱乐部细胞和纤毛细胞数量显著减少（均p < 0.001），中性粒细胞和嗜酸性粒细胞内型CRSwNP中基底细胞和杯状细胞数量分别增加（均p < 0.05）。在体外，与IFN-γ和IL-17A相比，il -13诱导的纤毛丢失和MUC5AC分泌显著（p < 0.05）， il -13处理的FCM细胞从SCGB1A1+β iv -微管蛋白+细胞转变为SCGB1A1+MUC5AC+细胞（p < 0.05）。此外，Dupilumab比AS1517499更有效地减轻il -13诱导的变化（均p < 0.05）。结论俱乐部细胞在鼻上皮修复中起重要作用，在CRSwNP中明显受损。这种损伤在il -13诱导的鼻上皮炎症模型中得到了强调，并且Dupilumab在恢复上皮修复机制方面的治疗效果进一步强调了这一点。
{"title":"Club Cells in Nasal Epithelial Repair: Insights From an IL-13-Induced Inflammatory Model.","authors":"Zhi-Qun Huang,Jing Liu,Jing Ye,Li-Ying Sun,Hsiao Hui Ong,Yang Peng,Bing-Qi Lin,Jun-Hao Tu,Ke-Shuang Wang,Yi-Shan Xiong,Qing Luo,Mark Thong,Yu Xu,De-Yun Wang","doi":"10.1111/all.70115","DOIUrl":"https://doi.org/10.1111/all.70115","url":null,"abstract":"BACKGROUNDClub cells, originating from basal cells, can differentiate into ciliated or goblet cells in the lower respiratory tract, but their role in nasal epithelium during chronic rhinosinusitis with nasal polyps (CRSwNP) is not well understood. We aim to investigate the role of club cells in CRSwNP and their biological mechanism in an IL-13-induced inflammation model of human nasal epithelial cells (HNECs).METHODSCRSwNP was classified into four endotypes (N-E-, N+E-, N-E+, and N+E+) based on neutrophil and eosinophil infiltration. The expression of basal (TP63+), club (SCGB1A1+), ciliated (βIV-tubulin+), and goblet cells (MUC5AC+) was assessed in healthy controls (n = 23) and CRSwNP (n = 73) using RT-qPCR, western blot (WB), and immunofluorescence. The effects of IL-13, Dupilumab, and STAT6 inhibitor (AS1517499) on cell differentiation were investigated in HNECs (n = 9) through RT-qPCR, WB, and flow cytometry (FCM).RESULTSClub and ciliated cells significantly decreased in four endotypes of CRSwNP (all p < 0.001), while basal and goblet cells increased in neutrophilic and eosinophilic CRSwNP, respectively (all p < 0.05). In vitro, IL-13-induced significant cilia loss and MUC5AC secretion compared to IFN-γ and IL-17A (all p < 0.05), and FCM revealed a shift from SCGB1A1+βIV-tubulin+ to SCGB1A1+MUC5AC+ cells by IL-13-treated (all p < 0.05). Furthermore, Dupilumab mitigated IL-13-induced changes more effectively than AS1517499 (all p < 0.05).CONCLUSIONSClub cells are crucial in nasal epithelial repair, which is notably compromised in CRSwNP. This impairment is highlighted in an IL-13-induced inflammation model of nasal epithelium and further underscored by the therapeutic effect of Dupilumab in restoring epithelial repair mechanisms.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"129 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338726","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}
BACKGROUNDAsthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protection against asthma and allergies. This study investigated the therapeutic potential of farm dust extract (FDE) in a murine model of allergic asthma when administered after sensitization and during allergen challenge, mimicking a secondary prevention or early interventional treatment approach.METHODSWe used an ovalbumin (OVA)-induced asthma model to evaluate FDE effects on airway eosinophilia, airway hyperresponsiveness (AHR), mucus production, and IgE levels. Mechanistic studies assessed regulatory T cells (Tregs), dendritic cell phenotype, epithelial barrier integrity, and cytokine signaling. Complementary experiments were performed in peripheral blood mononuclear cells (PBMCs) from asthmatic donors.RESULTSFDE significantly reduced airway inflammation and AHR, with secondary prevention effects comparable to systemic dexamethasone. FDE enhanced Treg frequency and CTLA-4 expression, modulated dendritic cell MHC-II and PD-L1 expression, and promoted an immunoregulatory environment. It also restored epithelial barrier integrity and increased IL-33 release, supporting Treg activation. In asthmatic PBMCs, FDE increased Tregs, reduced Th2 cells, and suppressed CIITA, suggesting similar immune-regulatory effects. Interactions among IL-33, amphiregulin (AREG), and Tregs highlighted a mechanism reinforcing immune-epithelial homeostasis.CONCLUSIONFDE administered after sensitization and during allergen challenge mitigated key asthma features in mice and showed translational potential in human cells, supporting its development as a novel, environmentally derived immunomodulatory strategy.
{"title":"The Therapeutic Potential of Farm Dust Extracts in a Mouse Model of Eosinophilic Inflammation.","authors":"Rabia Ülkü Korkmaz,Jimmy Omony,Xiaomei Tan,Markus Klotz,Guilherme Dragunas,Sirui Chen,Soni Shankhwar,Zeynep Ertüz,Christoph Müller,Mohab Ragab,Aicha Jeridi,Romina Augustin,Janna Nawroth,Theodore S Kapellos,Bettina Rankl,Ali Önder Yildirim,Erika von Mutius","doi":"10.1111/all.70121","DOIUrl":"https://doi.org/10.1111/all.70121","url":null,"abstract":"BACKGROUNDAsthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protection against asthma and allergies. This study investigated the therapeutic potential of farm dust extract (FDE) in a murine model of allergic asthma when administered after sensitization and during allergen challenge, mimicking a secondary prevention or early interventional treatment approach.METHODSWe used an ovalbumin (OVA)-induced asthma model to evaluate FDE effects on airway eosinophilia, airway hyperresponsiveness (AHR), mucus production, and IgE levels. Mechanistic studies assessed regulatory T cells (Tregs), dendritic cell phenotype, epithelial barrier integrity, and cytokine signaling. Complementary experiments were performed in peripheral blood mononuclear cells (PBMCs) from asthmatic donors.RESULTSFDE significantly reduced airway inflammation and AHR, with secondary prevention effects comparable to systemic dexamethasone. FDE enhanced Treg frequency and CTLA-4 expression, modulated dendritic cell MHC-II and PD-L1 expression, and promoted an immunoregulatory environment. It also restored epithelial barrier integrity and increased IL-33 release, supporting Treg activation. In asthmatic PBMCs, FDE increased Tregs, reduced Th2 cells, and suppressed CIITA, suggesting similar immune-regulatory effects. Interactions among IL-33, amphiregulin (AREG), and Tregs highlighted a mechanism reinforcing immune-epithelial homeostasis.CONCLUSIONFDE administered after sensitization and during allergen challenge mitigated key asthma features in mice and showed translational potential in human cells, supporting its development as a novel, environmentally derived immunomodulatory strategy.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"52 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338730","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}
BACKGROUNDMastocytosis is a clonal mast cell disorder (CMD) characterized by the proliferation and accumulation of mast cells (MC) in different tissues. Anaphylaxis, resulting from massive MC activation and mediators' release, is reported in 22%-49% of mastocytosis cases, with drugs being potential triggers. Proper counseling on drug safety is crucial. We aim to demonstrate that, after a careful evaluation of clinical history and allergic work-up, drug provocation tests (DPT) are a safe and effective diagnostic tool in patients with CMD.METHODSWe enrolled 104 CMD patients with a suspicion of drug hypersensitivity reactions (DHR) or without known tolerated drugs and 100 control patients with DHR. The types of DHR and the results of DPT were compared between CMD and control groups.RESULTSIn both groups, previous DHR was mostly represented by skin reactions (46.4% in CMD and 82.9% in the control group); the most involved drugs were aminopenicillins and nonsteroidal anti-inflammatory drugs (NSAIDs). We performed 250 DPTs in the CMD group and 231 in the control group; challenges were well tolerated in both groups, except for 6 skin reactions: 1 in the CMD group (1.0%) and 5 in the control group (5%).CONCLUSIONDrug challenge is a safe and effective diagnostic tool in patients with CMD. Moreover, patients that have never had adverse reactions to NSAIDs or antibiotics before the diagnosis of CMD do not need to undergo challenge tests. In contrast, patients with a history of reactions should avoid the culprit drugs and undergo DPT to identify a safe alternative drug.
{"title":"Safety of Drug Provocation Tests in Adults With and Without Clonal Mast Cell Disorders.","authors":"Francesca Nalin,Bianca Olivieri,Francesco Olivieri,Elisa Olivieri,Roberta Zanotti,Ilaria Tanasi,Andrea Bernardelli,Massimiliano Bonifacio,Francesca Norelli,Giorgia Marta,Valentina Gueli,Giovanna Sfriso,Patrizia Bonadonna","doi":"10.1111/all.70113","DOIUrl":"https://doi.org/10.1111/all.70113","url":null,"abstract":"BACKGROUNDMastocytosis is a clonal mast cell disorder (CMD) characterized by the proliferation and accumulation of mast cells (MC) in different tissues. Anaphylaxis, resulting from massive MC activation and mediators' release, is reported in 22%-49% of mastocytosis cases, with drugs being potential triggers. Proper counseling on drug safety is crucial. We aim to demonstrate that, after a careful evaluation of clinical history and allergic work-up, drug provocation tests (DPT) are a safe and effective diagnostic tool in patients with CMD.METHODSWe enrolled 104 CMD patients with a suspicion of drug hypersensitivity reactions (DHR) or without known tolerated drugs and 100 control patients with DHR. The types of DHR and the results of DPT were compared between CMD and control groups.RESULTSIn both groups, previous DHR was mostly represented by skin reactions (46.4% in CMD and 82.9% in the control group); the most involved drugs were aminopenicillins and nonsteroidal anti-inflammatory drugs (NSAIDs). We performed 250 DPTs in the CMD group and 231 in the control group; challenges were well tolerated in both groups, except for 6 skin reactions: 1 in the CMD group (1.0%) and 5 in the control group (5%).CONCLUSIONDrug challenge is a safe and effective diagnostic tool in patients with CMD. Moreover, patients that have never had adverse reactions to NSAIDs or antibiotics before the diagnosis of CMD do not need to undergo challenge tests. In contrast, patients with a history of reactions should avoid the culprit drugs and undergo DPT to identify a safe alternative drug.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"19 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331633","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}
BACKGROUNDThaumatin-like proteins (TLPs) are conserved plant pathogenesis-related proteins with IgE-binding capacity, but their clinical relevance remains poorly defined. Unlike well-characterized panallergens, TLPs are underrepresented in diagnostic panels, and their role in food allergy is largely unexplored.OBJECTIVETo assess the prevalence, quantitative IgE levels, co-sensitization patterns, and clinical significance of IgE reactivity to two TLPs-Act d 2 (kiwi) and Mal d 2 (apple)-in a large Italian allergic cohort.METHODSWe conducted a cross-sectional study of 7176 consecutive patients referred to Italian tertiary allergy centers. Specific IgE to TLPs and other plant allergens was measured using ALEX2. Clinical outcomes were evaluated, and associations with IgE levels and co-sensitizations were examined using multivariate models. ROC analyses were applied to evaluate the discriminatory ability of Act d 2 IgE for clinical severity.RESULTSTLP sensitization occurred in 137 patients (1.9%), predominantly to Act d 2. Isolated TLP sensitization was rare (n = 20) and associated with low IgE levels (mean 0.61 ± 0.98 kUA/L) and minimal symptoms. Co-sensitized patients (n = 117) had higher and more variable IgE levels (mean 1.41 ± 3.49 kUA/L) and experienced more clinically relevant reactions, including oral allergy syndrome and food-dependent exercise-induced anaphylaxis. ROC analyses indicated limited discriminatory power of Act d 2 IgE for predicting reaction severity (AUC 0.51-0.61). Multivariate adjustment confirmed no independent association between TLP-specific IgE and moderate or severe symptoms.CONCLUSIONSTLP sensitization is uncommon and generally clinically silent when isolated. Co-sensitization with other panallergens appears to drive allergic manifestations. Quantitative TLP-specific IgE alone provides limited predictive value, emphasizing the importance of integrating molecular diagnostics with clinical phenotyping in precision allergy management.
{"title":"Thaumatin-Like Proteins in Molecular Allergy Diagnostics: Uncommon Co-Sensitized, and Clinically Inconspicuous? Insights From an Italian Cohort.","authors":"Enrico Scala,Damiano Abeni,Mauro Giani,Valeria Villella,Elisabetta Caprini,Ignazio Brusca,Lorenzo Cecchi,Danilo Villalta,Riccardo Asero","doi":"10.1111/all.70114","DOIUrl":"https://doi.org/10.1111/all.70114","url":null,"abstract":"BACKGROUNDThaumatin-like proteins (TLPs) are conserved plant pathogenesis-related proteins with IgE-binding capacity, but their clinical relevance remains poorly defined. Unlike well-characterized panallergens, TLPs are underrepresented in diagnostic panels, and their role in food allergy is largely unexplored.OBJECTIVETo assess the prevalence, quantitative IgE levels, co-sensitization patterns, and clinical significance of IgE reactivity to two TLPs-Act d 2 (kiwi) and Mal d 2 (apple)-in a large Italian allergic cohort.METHODSWe conducted a cross-sectional study of 7176 consecutive patients referred to Italian tertiary allergy centers. Specific IgE to TLPs and other plant allergens was measured using ALEX2. Clinical outcomes were evaluated, and associations with IgE levels and co-sensitizations were examined using multivariate models. ROC analyses were applied to evaluate the discriminatory ability of Act d 2 IgE for clinical severity.RESULTSTLP sensitization occurred in 137 patients (1.9%), predominantly to Act d 2. Isolated TLP sensitization was rare (n = 20) and associated with low IgE levels (mean 0.61 ± 0.98 kUA/L) and minimal symptoms. Co-sensitized patients (n = 117) had higher and more variable IgE levels (mean 1.41 ± 3.49 kUA/L) and experienced more clinically relevant reactions, including oral allergy syndrome and food-dependent exercise-induced anaphylaxis. ROC analyses indicated limited discriminatory power of Act d 2 IgE for predicting reaction severity (AUC 0.51-0.61). Multivariate adjustment confirmed no independent association between TLP-specific IgE and moderate or severe symptoms.CONCLUSIONSTLP sensitization is uncommon and generally clinically silent when isolated. Co-sensitization with other panallergens appears to drive allergic manifestations. Quantitative TLP-specific IgE alone provides limited predictive value, emphasizing the importance of integrating molecular diagnostics with clinical phenotyping in precision allergy management.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"13 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338732","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}
BACKGROUNDThymic stromal lymphopoietin (TSLP) is a master regulator of type 2 immune responses; however, the associations between serum TSLP and the characteristics of adult asthma have not been fully clarified. The aim of this study was to determine the characteristics of adult asthma with high serum TSLP and explore TSLP's association with the late-onset eosinophilic asthma phenotype.METHODSBaseline data of the TNH-Azma study (a real-world observational cohort study conducted in Japan on 1344 patients with asthma from 30 hospitals) was used and serum cytokines were measured. Patients were stratified into quartile groups based on the baseline serum TSLP levels, and their clinical characteristics were compared. Multivariable regression analyses were used to determine clinical variables associated with serum TSLP and cytokines associated with the late-onset eosinophilic asthma phenotype.RESULTSPatients with TSLP-high asthma were older, late-onset, eosinophilic, and less atopic; had a higher BMI; more smoking history; and more asthma-COPD overlap, sleep apnea syndrome (SAS), hypertension, and heart disease. They also exhibited lower lung function with worse asthma symptoms and were more frequently on oral corticosteroids. Multivariable regression analyses adjusted for age and sex demonstrated that a high TSLP level was positively associated with later asthma onset, longer asthma duration, hypertension, higher blood eosinophils, BMI, smoking history, use of biologics, SAS, and high Fres, and was negatively associated with pollinosis. Among the serum cytokines, TSLP exhibited the strongest association with late-onset, eosinophilic asthma.CONCLUSIONHigh serum TSLP is a distinctive feature of late-onset, long-duration, eosinophilic asthma. Patients with asthma with this feature may be a unique target population for specific asthma therapy.
{"title":"High Serum TSLP Is Characteristic of Late-Onset, Long-Duration, Eosinophilic Asthma.","authors":"Maho Suzukawa,Ken Ohta,Hiroyuki Tashimo,Osamu Narumoto,Hiroya Hashimoto,Toshiyuki Kita,Hazuki Takato,Hiroyuki Nagase,Konomi Kobayashi,Masao Yamaguchi,Masahiro Abe,Ryoji Ito,Takeo Endo,Hidetoshi Yanai,Kenji Chibana,Nobuyuki Hizawa,Yasushi Tanimoto,Koichi Takagi,Tsuyoshi Oguma,Norihiro Harada,Hironori Sagara,Aika Kato,Shohei Takata,Yuko Komase,Kentaro Hyodo,Kazuto Matsunaga,Kazuyuki Tsujino,Akio Niimi,Kentaro Wakamatsu,Hisatoshi Sugiura,Yumi Sakakibara,Mitsuhiro Kamimura,Yoko Shibata,Goh Tanaka,Keitaro Nakamoto,Shinji Tamaki,Yoshiaki Minakata,Takanori Numata,Akiko M Saito,Nobuyuki Kobayashi,Masami Taniguchi, ","doi":"10.1111/all.70109","DOIUrl":"https://doi.org/10.1111/all.70109","url":null,"abstract":"BACKGROUNDThymic stromal lymphopoietin (TSLP) is a master regulator of type 2 immune responses; however, the associations between serum TSLP and the characteristics of adult asthma have not been fully clarified. The aim of this study was to determine the characteristics of adult asthma with high serum TSLP and explore TSLP's association with the late-onset eosinophilic asthma phenotype.METHODSBaseline data of the TNH-Azma study (a real-world observational cohort study conducted in Japan on 1344 patients with asthma from 30 hospitals) was used and serum cytokines were measured. Patients were stratified into quartile groups based on the baseline serum TSLP levels, and their clinical characteristics were compared. Multivariable regression analyses were used to determine clinical variables associated with serum TSLP and cytokines associated with the late-onset eosinophilic asthma phenotype.RESULTSPatients with TSLP-high asthma were older, late-onset, eosinophilic, and less atopic; had a higher BMI; more smoking history; and more asthma-COPD overlap, sleep apnea syndrome (SAS), hypertension, and heart disease. They also exhibited lower lung function with worse asthma symptoms and were more frequently on oral corticosteroids. Multivariable regression analyses adjusted for age and sex demonstrated that a high TSLP level was positively associated with later asthma onset, longer asthma duration, hypertension, higher blood eosinophils, BMI, smoking history, use of biologics, SAS, and high Fres, and was negatively associated with pollinosis. Among the serum cytokines, TSLP exhibited the strongest association with late-onset, eosinophilic asthma.CONCLUSIONHigh serum TSLP is a distinctive feature of late-onset, long-duration, eosinophilic asthma. Patients with asthma with this feature may be a unique target population for specific asthma therapy.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"200 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331965","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}
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