Xin Yan, Xinyang Xie, Xuemei Gao, Munire Tayier, Yi Dong, Yifeng Yang, Zhongmin Liao, Sin Tong Cheang, Wenjing Jiang, Naiyu Lin, Lu Ai, Xingqi Zhang, Yanting Ye
Background Alopecia areata (AA) frequently co‐occurs with atopic dermatitis (AD; AA‐AD); however, AA‐AD's features remain unclear. Objective To elucidate the clinical and immunological features of AA‐AD. Methods Retrospective analysis of data from 123 AA‐AD patients, 119 non‐atopic AA patients, and 126 AD patients (2011–2024). Peripheral blood mononuclear cells (PBMCs), plasma, and scalp tissues from patients and healthy controls (HC) were examined by flow cytometry, multiplex cytokine assays, and immunofluorescence. Results Clinically, AA‐AD patients were younger than non‐atopic AA and AD‐only patients, showed more severe alopecia and longer duration, but milder eczema, and exhibited higher dust‐mite allergy, total IgE (tIgE), and Eos counts/percentages than non‐atopic AA, while showing more intrinsic AD and lower tIgE and Eos counts/percentages than AD‐only patients. AA severity and duration were positively correlated with those of AD. Compared with AA‐AD patients with AA‐first onset and AA with intrinsic AD (AA‐IAD) patients, AA‐AD patients with AD‐first onset and AA with extrinsic AD (AA‐EAD) patients were younger, had more severe eczema, higher tIgE levels, and dust‐mite allergy. Compared with the non‐atopic AA group and HC, the AA‐AD group showed elevated plasma IL‐4/6/10/13 levels and increased Th2 cells and ILC2s (group 2 innate lymphoid cells) proportions in PBMCs, along with their IL‐13 production, all of which were positively correlated with AA course. AA‐AD scalp also showed that Th2 cells and ILC2s were most abundant. Conclusion AA‐AD defines a distinct clinical‐immunologic endotype of AA. AA and AD exhibit an asymmetric but bilateral interaction driven by Th2/ILC2s‐IL‐13‐centered pathways, representing key mechanisms and targets for precision therapy.
{"title":"Investigation of Clinical and Immunological Features of Alopecia Areata With Comorbid Atopic Dermatitis","authors":"Xin Yan, Xinyang Xie, Xuemei Gao, Munire Tayier, Yi Dong, Yifeng Yang, Zhongmin Liao, Sin Tong Cheang, Wenjing Jiang, Naiyu Lin, Lu Ai, Xingqi Zhang, Yanting Ye","doi":"10.1111/all.70534","DOIUrl":"https://doi.org/10.1111/all.70534","url":null,"abstract":"Background Alopecia areata (AA) frequently co‐occurs with atopic dermatitis (AD; AA‐AD); however, AA‐AD's features remain unclear. Objective To elucidate the clinical and immunological features of AA‐AD. Methods Retrospective analysis of data from 123 AA‐AD patients, 119 non‐atopic AA patients, and 126 <jats:sc>AD</jats:sc> patients (2011–2024). Peripheral blood mononuclear cells (PBMCs), plasma, and scalp tissues from patients and healthy controls (HC) were examined by flow cytometry, multiplex cytokine assays, and immunofluorescence. Results Clinically, AA‐AD patients were younger than non‐atopic AA and AD‐only patients, showed more severe alopecia and longer duration, but milder eczema, and exhibited higher dust‐mite allergy, total IgE (tIgE), and Eos counts/percentages than non‐atopic AA, while showing more intrinsic AD and lower tIgE and Eos counts/percentages than AD‐only patients. AA severity and duration were positively correlated with those of AD. Compared with AA‐AD patients with AA‐first onset and AA with intrinsic AD (AA‐IAD) patients, AA‐AD patients with AD‐first onset and AA with extrinsic AD (AA‐EAD) patients were younger, had more severe eczema, higher tIgE levels, and dust‐mite allergy. Compared with the non‐atopic AA group and HC, the AA‐AD group showed elevated plasma IL‐4/6/10/13 levels and increased Th2 cells and ILC2s (group 2 innate lymphoid cells) proportions in PBMCs, along with their IL‐13 production, all of which were positively correlated with AA course. AA‐AD scalp also showed that Th2 cells and ILC2s were most abundant. Conclusion AA‐AD defines a distinct clinical‐immunologic endotype of AA. AA and AD exhibit an asymmetric but bilateral interaction driven by Th2/ILC2s‐IL‐13‐centered pathways, representing key mechanisms and targets for precision therapy.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"28 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218451","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}
Paula Montero, Ines Roger, Anselm Morell, Rubén Serrano‐Santos, Oscar Villarroya‐Palomo, Miguel Armengot, Julio Cortijo, Javier Milara
Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which persistent remodeling and fibrosis may contribute to corticosteroid refractoriness. Membrane‐tethered mucins, particularly MUC16, may regulate profibrotic and steroid‐response pathways. Objectives To determine whether MUC16 is associated with fibrosis and corticosteroid insensitivity in CRSwNP and to define its functional effects in fibroblasts and epithelial cells. Methods Nasal polyp tissue from CRSwNP subgroups, including oral corticosteroid‐resistant patients, was analyzed by histology, immunohistochemistry, hydroxyproline quantification, and RT‐qPCR. Primary nasal polyp fibroblasts and epithelial cells, and MRC5, BEAS2B, and HeLa cells, were stimulated with TGF‐β1 or LPS and treated with dexamethasone. MUC16 was silenced with siRNA, and profibrotic and glucocorticoid‐response pathways were evaluated. Results Oral corticosteroid‐resistant polyps showed the highest fibrosis (collagen, α‐SMA‐positive fibroblasts, TGF‐β1, hydroxyproline), despite not being the most eosinophilic. MUC16 increased in these polyps and correlated with hydroxyproline. Their fibroblasts, overexpressing MUC16, showed reduced dexamethasone inhibition of TGF‐β1‐induced collagen I and proliferation. MUC16 silencing reduced phospho‐SMAD3 and Smad‐binding element activity, restored dexamethasone sensitivity, and reduced proliferation. In epithelium, MUC16 silencing enhanced dexamethasone suppression of LPS‐induced IL‐6, reduced STAT3 phosphorylation, and increased glucocorticoid response element activity, GR Ser211 phosphorylation, and MKP1 induction. Conclusions In human polyp tissue, MUC16 is associated with a fibrotic, corticosteroid‐insensitive CRSwNP phenotype, whereas its causal link with impaired glucocorticoid signaling is supported by in vitro loss‐of‐function experiments. MUC16 may represent a candidate biomarker and potential therapeutic target in refractory CRSwNP, although prospective validation as an endotype‐defining biomarker is still required.
{"title":"MUC16 Defines a Fibrotic Endotype With Corticosteroid Insensitivity in Nasal Polyps","authors":"Paula Montero, Ines Roger, Anselm Morell, Rubén Serrano‐Santos, Oscar Villarroya‐Palomo, Miguel Armengot, Julio Cortijo, Javier Milara","doi":"10.1111/all.70541","DOIUrl":"https://doi.org/10.1111/all.70541","url":null,"abstract":"Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which persistent remodeling and fibrosis may contribute to corticosteroid refractoriness. Membrane‐tethered mucins, particularly MUC16, may regulate profibrotic and steroid‐response pathways. Objectives To determine whether MUC16 is associated with fibrosis and corticosteroid insensitivity in CRSwNP and to define its functional effects in fibroblasts and epithelial cells. Methods Nasal polyp tissue from CRSwNP subgroups, including oral corticosteroid‐resistant patients, was analyzed by histology, immunohistochemistry, hydroxyproline quantification, and RT‐qPCR. Primary nasal polyp fibroblasts and epithelial cells, and MRC5, BEAS2B, and HeLa cells, were stimulated with TGF‐β1 or LPS and treated with dexamethasone. MUC16 was silenced with siRNA, and profibrotic and glucocorticoid‐response pathways were evaluated. Results Oral corticosteroid‐resistant polyps showed the highest fibrosis (collagen, α‐SMA‐positive fibroblasts, TGF‐β1, hydroxyproline), despite not being the most eosinophilic. MUC16 increased in these polyps and correlated with hydroxyproline. Their fibroblasts, overexpressing MUC16, showed reduced dexamethasone inhibition of TGF‐β1‐induced collagen I and proliferation. MUC16 silencing reduced phospho‐SMAD3 and Smad‐binding element activity, restored dexamethasone sensitivity, and reduced proliferation. In epithelium, MUC16 silencing enhanced dexamethasone suppression of LPS‐induced IL‐6, reduced STAT3 phosphorylation, and increased glucocorticoid response element activity, GR Ser211 phosphorylation, and MKP1 induction. Conclusions In human polyp tissue, MUC16 is associated with a fibrotic, corticosteroid‐insensitive CRSwNP phenotype, whereas its causal link with impaired glucocorticoid signaling is supported by in vitro loss‐of‐function experiments. MUC16 may represent a candidate biomarker and potential therapeutic target in refractory CRSwNP, although prospective validation as an endotype‐defining biomarker is still required.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"239 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198932","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}
Franziska U. Nordström, Malin Lindstedt, Lennart Greiff, Jonas S. Erjefält
{"title":"Established Tissue Eosinophilia is Not Synonymous With Ongoing Local Type 2 Cytokine Activity","authors":"Franziska U. Nordström, Malin Lindstedt, Lennart Greiff, Jonas S. Erjefält","doi":"10.1111/all.70544","DOIUrl":"https://doi.org/10.1111/all.70544","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"30 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198929","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}
Zhouxian Pan, Zhirong Du, Janice A. Layhadi, Bin Yang, Mingle Tian, Juan Liu, Lin Chen, Shengyang Yao, Yan Feng, Lisha Li, Xingyu Zhou, Sainan Bian, Yu Shi, Anqi Li, Lianglu Wang, Kai Guan, Jia Yin, Mohamed H. Shamji
{"title":"A Novel Phenotype of Mugwort‐Associated Delayed Gastrointestinal‐Onset Anaphylaxis With Nasal‐Ocular Involvement","authors":"Zhouxian Pan, Zhirong Du, Janice A. Layhadi, Bin Yang, Mingle Tian, Juan Liu, Lin Chen, Shengyang Yao, Yan Feng, Lisha Li, Xingyu Zhou, Sainan Bian, Yu Shi, Anqi Li, Lianglu Wang, Kai Guan, Jia Yin, Mohamed H. Shamji","doi":"10.1111/all.70515","DOIUrl":"https://doi.org/10.1111/all.70515","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"17 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172520","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}
Xiaojie Wu, Jingjing Fan, Huiyuan Ding, Shiwen Li, Rui Ye, Honghao Yang, Zheng Ma, Chao Ji, Qing Chang, Yuhong Zhao, Chuming Zhou, Li Zhao, Yang Xia
Introduction While eosinophils are established pathogenic drivers and therapeutic targets in asthma, their role in chronic obstructive pulmonary disease (COPD) remains conflicting. This study aimed to investigate the bidirectional associations of eosinophils with COPD and asthma, and to elucidate the potential distinct underlying mechanisms. Methods In 302,370 UK Biobank participants, multivariable‐adjusted Cox proportional hazards models assessed associations between blood eosinophil counts and incident COPD, asthma, and asthma COPD overlap (ACO). Bidirectional two‐sample Mendelian randomization (MR) tested causality. Among 32,121 participants with available baseline Olink proteomic data, proteomic profiling characterized eosinophil‐associated plasma protein signatures and their associations with disease risk. Results During approximately 13.5 years of follow‐up, elevated blood eosinophils were associated with increased risks of COPD, asthma, and ACO. Unlike asthma, pre‐existing COPD did not predict subsequent eosinophil elevation. MR indicated a unidirectional effect of eosinophils on COPD but bidirectional causality for asthma. Proteomics revealed a broader protein interaction network in COPD (378 proteins) than in asthma (70 proteins). Exploratory mediation analyses, assuming an eosinophil‐to‐protein direction, estimated that the eosinophil‐associated proteomic signature statistically accounted for 87.8% of the association with COPD ( p = 0.076) and 59.1% of the association with asthma ( p < 0.001). Among these proteins, COPD‐associated mediators were linked to a broad and intricately woven inflammatory network, in contrast to the more streamlined network that is mainly confined to Type 2 inflammation seen in asthma. Conclusion Although elevated eosinophil levels are associated with increased COPD risk, their pathogenic role—embedded within a complex inflammatory network—differs fundamentally from the Th2‐centric inflammatory pathway characteristic of asthma. This observational study suggests that eosinophilic COPD is not simply a surrogate for asthma‐like Type 2 inflammation.
{"title":"Not Just Th 2: Eosinophil‐Associated Proteomic Networks Reveal Fundamental Differences Between COPD and Asthma","authors":"Xiaojie Wu, Jingjing Fan, Huiyuan Ding, Shiwen Li, Rui Ye, Honghao Yang, Zheng Ma, Chao Ji, Qing Chang, Yuhong Zhao, Chuming Zhou, Li Zhao, Yang Xia","doi":"10.1111/all.70538","DOIUrl":"https://doi.org/10.1111/all.70538","url":null,"abstract":"Introduction While eosinophils are established pathogenic drivers and therapeutic targets in asthma, their role in chronic obstructive pulmonary disease (COPD) remains conflicting. This study aimed to investigate the bidirectional associations of eosinophils with COPD and asthma, and to elucidate the potential distinct underlying mechanisms. Methods In 302,370 UK Biobank participants, multivariable‐adjusted Cox proportional hazards models assessed associations between blood eosinophil counts and incident COPD, asthma, and asthma COPD overlap (ACO). Bidirectional two‐sample Mendelian randomization (MR) tested causality. Among 32,121 participants with available baseline Olink proteomic data, proteomic profiling characterized eosinophil‐associated plasma protein signatures and their associations with disease risk. Results During approximately 13.5 years of follow‐up, elevated blood eosinophils were associated with increased risks of COPD, asthma, and ACO. Unlike asthma, pre‐existing COPD did not predict subsequent eosinophil elevation. MR indicated a unidirectional effect of eosinophils on COPD but bidirectional causality for asthma. Proteomics revealed a broader protein interaction network in COPD (378 proteins) than in asthma (70 proteins). Exploratory mediation analyses, assuming an eosinophil‐to‐protein direction, estimated that the eosinophil‐associated proteomic signature statistically accounted for 87.8% of the association with COPD ( <jats:italic>p</jats:italic> = 0.076) and 59.1% of the association with asthma ( <jats:italic>p</jats:italic> < 0.001). Among these proteins, COPD‐associated mediators were linked to a broad and intricately woven inflammatory network, in contrast to the more streamlined network that is mainly confined to Type 2 inflammation seen in asthma. Conclusion Although elevated eosinophil levels are associated with increased COPD risk, their pathogenic role—embedded within a complex inflammatory network—differs fundamentally from the Th2‐centric inflammatory pathway characteristic of asthma. This observational study suggests that eosinophilic COPD is not simply a surrogate for asthma‐like Type 2 inflammation.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"8 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140454","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}
Ludger Klimek, María José Torres, Jean Bousquet, Giorgio Walter Canonica, Mohamed H. Shamji, Sven Becker, Karl‐Christian Bergmann, Friederike Bärhold, Jan Hagemann, Uwe Berger, Markus Berger, Stefania Arasi, Markus Ollert, Oscar Palomares, Carmen Rondon, Mattia Giovannini, Petra Zieglmayer
Grass pollen, the most clinically relevant outdoor aeroallergen in Europe and worldwide, presents a complex challenge due to the diverse nature of its subspecies. This diversity complicates the interpretation of their contribution to the overall pollen burden during the grass pollen season and the selection of the appropriate allergen immunotherapy. Almost all species of the Pooideae subfamily share important major allergens, namely the allergens of Group 1 and 5, leading to a high level of cross‐reactivity at the IgE level. However, the presence of a multitude of additional minor allergens and species‐specific epitopes adds to the complexity. Timothy ( Phleum pratense ), previously considered the most relevant allergen source among grass species, is found during the late‐blooming grass pollen season, while symptom severity and pollen concentrations already show several peaks during the early‐blooming grass and main grass pollen seasons. Current data suggest a limited regional relevance of timothy grass during the natural grass pollen season in southern Europe from both the aerobiology and allergy perspectives. This review aims to discuss the latest evidence supporting a broad‐spectrum approach to best reflect natural grass pollen exposure in allergen immunotherapy, presenting a complex but crucial aspect of allergology.
{"title":"Natural Diversity of Grass Pollen in Europe—An EAACI Perspective","authors":"Ludger Klimek, María José Torres, Jean Bousquet, Giorgio Walter Canonica, Mohamed H. Shamji, Sven Becker, Karl‐Christian Bergmann, Friederike Bärhold, Jan Hagemann, Uwe Berger, Markus Berger, Stefania Arasi, Markus Ollert, Oscar Palomares, Carmen Rondon, Mattia Giovannini, Petra Zieglmayer","doi":"10.1111/all.70536","DOIUrl":"https://doi.org/10.1111/all.70536","url":null,"abstract":"Grass pollen, the most clinically relevant outdoor aeroallergen in Europe and worldwide, presents a complex challenge due to the diverse nature of its subspecies. This diversity complicates the interpretation of their contribution to the overall pollen burden during the grass pollen season and the selection of the appropriate allergen immunotherapy. Almost all species of the Pooideae subfamily share important major allergens, namely the allergens of Group 1 and 5, leading to a high level of cross‐reactivity at the IgE level. However, the presence of a multitude of additional minor allergens and species‐specific epitopes adds to the complexity. Timothy ( <jats:styled-content style=\"fixed-case\"> <jats:italic>Phleum pratense</jats:italic> </jats:styled-content> ), previously considered the most relevant allergen source among grass species, is found during the late‐blooming grass pollen season, while symptom severity and pollen concentrations already show several peaks during the early‐blooming grass and main grass pollen seasons. Current data suggest a limited regional relevance of timothy grass during the natural grass pollen season in southern Europe from both the aerobiology and allergy perspectives. This review aims to discuss the latest evidence supporting a broad‐spectrum approach to best reflect natural grass pollen exposure in allergen immunotherapy, presenting a complex but crucial aspect of allergology.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"12 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130336","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}
Airway epithelial barrier dysfunction is a central feature of asthma pathogenesis, yet the molecular mechanisms by which post-translational modifications regulate epithelial integrity remain incompletely understood. Fucosylation has emerged as a potential regulator of epithelial homeostasis across mucosal tissues.
Objective
We sought to investigate whether epithelial fucosylation contributes to allergen-induced barrier dysfunction and airway inflammation and to define their underlying mechanisms.
Methods
Fucosylation levels were assessed in saliva from children with asthma using mass spectrometry. Air-liquid interface epithelial cultures were used to assess barrier function by transepithelial electrical resistance, tight junction protein expression and cytokine release. Transcriptomic analyses were performed to identify dysregulated fucosylation pathways. Fut1 was selectively inhibited in vivo and in vitro using intratracheally delivered AAV6-encoded shRNA. Downstream targets were also evaluated by RNA sequencing.
Results
Fucosylation was significantly increased in saliva from children with asthma and in allergen-exposed mouse airways. Pharmacologic inhibition of fucosylation preserved epithelial barrier integrity, maintained junctional organization and reduced allergen-induced epithelial cytokine release. Transcriptomic profiling identified fucosylation as a major upregulated pathway, with increased expression of Fut1, Fut2, Fut7 and Fut9. Epithelial-specific Fut1 knockdown attenuated Th2-driven inflammation, preserved epithelial junctional architecture and suppressed alarmin release. Integrated analyses revealed 56 Fut1-dependent genes enriched in cell-adhesion pathways, including Cdh12, App, Ank3 and Cd9. Fut1-CDH12 protein interaction was confirmed by immunoprecipitation, and FUT1-dependent induction of CDH12 disrupted epithelial junctional organization and barrier function.
Conclusion
These findings identify the FUT1-CDH12 axis as a previously unrecognized epithelial mechanism promoting barrier dysfunction and allergic airway inflammation in asthma.
{"title":"Epithelial Fucosylation Drives Airway Barrier Dysfunction and Allergic Inflammation via a FUT1 -CDH12 Axis","authors":"Wenjing Gu, Xinxing Zhang, Yufeng Wang, Hui Wang, Yanyu He, Shengye Wen, Heting Dong, Qiuchi Shen, Minxuan Hu, Shuang Yang, Chuangli Hao, Peisong Gao","doi":"10.1111/all.70413","DOIUrl":"10.1111/all.70413","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Airway epithelial barrier dysfunction is a central feature of asthma pathogenesis, yet the molecular mechanisms by which post-translational modifications regulate epithelial integrity remain incompletely understood. Fucosylation has emerged as a potential regulator of epithelial homeostasis across mucosal tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We sought to investigate whether epithelial fucosylation contributes to allergen-induced barrier dysfunction and airway inflammation and to define their underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fucosylation levels were assessed in saliva from children with asthma using mass spectrometry. Air-liquid interface epithelial cultures were used to assess barrier function by transepithelial electrical resistance, tight junction protein expression and cytokine release. Transcriptomic analyses were performed to identify dysregulated fucosylation pathways. Fut1 was selectively inhibited in vivo and in vitro using intratracheally delivered AAV6-encoded shRNA. Downstream targets were also evaluated by RNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fucosylation was significantly increased in saliva from children with asthma and in allergen-exposed mouse airways. Pharmacologic inhibition of fucosylation preserved epithelial barrier integrity, maintained junctional organization and reduced allergen-induced epithelial cytokine release. Transcriptomic profiling identified fucosylation as a major upregulated pathway, with increased expression of Fut1, Fut2, Fut7 and Fut9. Epithelial-specific Fut1 knockdown attenuated Th2-driven inflammation, preserved epithelial junctional architecture and suppressed alarmin release. Integrated analyses revealed 56 Fut1-dependent genes enriched in cell-adhesion pathways, including <i>Cdh12</i>, <i>App</i>, <i>Ank3</i> and <i>Cd9</i>. Fut1-CDH12 protein interaction was confirmed by immunoprecipitation, and FUT1-dependent induction of CDH12 disrupted epithelial junctional organization and barrier function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings identify the FUT1-CDH12 axis as a previously unrecognized epithelial mechanism promoting barrier dysfunction and allergic airway inflammation in asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 10","pages":"3515-3532"},"PeriodicalIF":11.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262374","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}
Pub Date : 2026-10-08Epub Date: 2026-08-23DOI: 10.1111/all.70494
Tari Haahtela, Jaana I. Halonen, Hanna Haveri, Paula Hellemaa, Juha Jantunen, Erkka Valovirta, Tuula Vasankari, Mika J. Mäkelä
<p>World population explosion during the last century has accelerated urbanization and profoundly modified the environment and lifestyle for most of humankind. For a good reason, the public discussion is dominated by the major environmental health risks like global warming, nature loss, and pollution [<span>1</span>]. Nevertheless, negative thinking is causing indifference and hopelessness especially among young people. Humankind is one part of a broader ecosystem dependent on the state of other natural systems that bring both risks and protective benefits. Strengthening everyday exposure to protective factors can build immunological and mental resilience and promote healthier living.</p><p>Here, we provide examples from Finland of how nature-based measures can support allergy prevention and promote public health.</p><p>The newly presented EAACI guidelines with eight recommendations underline the importance of green space in urban environments for allergy & asthma prevention and management [<span>2</span>]. The recommendations address the prevention of new-onset sensitization and clinical symptoms, as well as improved disease management. The guidelines are based on a systematic review [<span>3</span>] and clinical experience making them credible in practice (Table 1). Many of the measures to improve nature contact seem self-evident but lack controlled intervention studies to validate the information for societal, healthcare and patient use.</p><p>The EAACI recommendations take pioneering steps from avoidance to boost immune tolerance, which may also pave the way to mitigate the urban epidemic of non-communicable diseases (NCDs). Targeted avoidance, however, will always stay in the armamentarium of clinicians to help their allergic patients [<span>4</span>].</p><p><i>The biodiversity hypothesis</i> emerged from the Karelia study in 2011–2012 highlighting the relation of natural immunity to environmental biodiversity [<span>5, 6</span>]. Based on the hypothesis, the Finnish Allergy Programme was a breakthrough in Finland for better allergy health with an impact on public health. Here, we present this and two other 10-year public health Programmes with defined goals and measures. In addition, two 3–4-year initiatives by patient and professional non-governmental organizations are also included in Figure 1.</p><p><i>The Finnish Allergy Programme</i> (2008–2018) was a nationwide, real-life initiative aimed at shifting from general avoidance towards tolerance through new guidelines, better disease management, and encouraging for nature contacts [<span>7</span>]. Over 10 years, the burden of allergic diseases reduced markedly with cumulative cost savings of € 1,2 billion in a population of 5,5 million. The Programme was adopted by the EU Best Practice Portal in 2022 and has been a model in Europe.</p><p><i>Nature Step to Health</i> (2022–2032) is a 10-year initiative for planetary health in the Lahti region [<span>8</span>]. The Wellbeing Services Co
{"title":"From Risks to Protection—Natural Strategy to Prevent Allergy and Support Public Health","authors":"Tari Haahtela, Jaana I. Halonen, Hanna Haveri, Paula Hellemaa, Juha Jantunen, Erkka Valovirta, Tuula Vasankari, Mika J. Mäkelä","doi":"10.1111/all.70494","DOIUrl":"10.1111/all.70494","url":null,"abstract":"<p>World population explosion during the last century has accelerated urbanization and profoundly modified the environment and lifestyle for most of humankind. For a good reason, the public discussion is dominated by the major environmental health risks like global warming, nature loss, and pollution [<span>1</span>]. Nevertheless, negative thinking is causing indifference and hopelessness especially among young people. Humankind is one part of a broader ecosystem dependent on the state of other natural systems that bring both risks and protective benefits. Strengthening everyday exposure to protective factors can build immunological and mental resilience and promote healthier living.</p><p>Here, we provide examples from Finland of how nature-based measures can support allergy prevention and promote public health.</p><p>The newly presented EAACI guidelines with eight recommendations underline the importance of green space in urban environments for allergy & asthma prevention and management [<span>2</span>]. The recommendations address the prevention of new-onset sensitization and clinical symptoms, as well as improved disease management. The guidelines are based on a systematic review [<span>3</span>] and clinical experience making them credible in practice (Table 1). Many of the measures to improve nature contact seem self-evident but lack controlled intervention studies to validate the information for societal, healthcare and patient use.</p><p>The EAACI recommendations take pioneering steps from avoidance to boost immune tolerance, which may also pave the way to mitigate the urban epidemic of non-communicable diseases (NCDs). Targeted avoidance, however, will always stay in the armamentarium of clinicians to help their allergic patients [<span>4</span>].</p><p><i>The biodiversity hypothesis</i> emerged from the Karelia study in 2011–2012 highlighting the relation of natural immunity to environmental biodiversity [<span>5, 6</span>]. Based on the hypothesis, the Finnish Allergy Programme was a breakthrough in Finland for better allergy health with an impact on public health. Here, we present this and two other 10-year public health Programmes with defined goals and measures. In addition, two 3–4-year initiatives by patient and professional non-governmental organizations are also included in Figure 1.</p><p><i>The Finnish Allergy Programme</i> (2008–2018) was a nationwide, real-life initiative aimed at shifting from general avoidance towards tolerance through new guidelines, better disease management, and encouraging for nature contacts [<span>7</span>]. Over 10 years, the burden of allergic diseases reduced markedly with cumulative cost savings of € 1,2 billion in a population of 5,5 million. The Programme was adopted by the EU Best Practice Portal in 2022 and has been a model in Europe.</p><p><i>Nature Step to Health</i> (2022–2032) is a 10-year initiative for planetary health in the Lahti region [<span>8</span>]. The Wellbeing Services Co","PeriodicalId":122,"journal":{"name":"Allergy","volume":"81 10","pages":"3411-3413"},"PeriodicalIF":11.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768941","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}
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