Journal of Allergy and Clinical Immunology最新文献

{"title":"Exploring geographic differences in IgE response through network and manifold analyses","authors":"Alex Cucco PhD ,&nbsp;Neil Pearce PhD ,&nbsp;Angela Simpson MD, PhD ,&nbsp;Lucy Pembrey PhD ,&nbsp;Harriet Mpairwe PhD ,&nbsp;Camila A. Figueiredo PhD ,&nbsp;Philip J. Cooper PhD ,&nbsp;Jeroen Douwes PhD ,&nbsp;Collin Brooks PhD ,&nbsp;Ian M. Adcock PhD ,&nbsp;Nazanin Zounemat Kermani PhD ,&nbsp;Graham D.M. Roberts MD PhD ,&nbsp;Clare S. Murray MD ,&nbsp;Adnan Custovic MD, PhD, FMedSci ,&nbsp;Sara Fontanella PhD","doi":"10.1016/j.jaci.2025.05.032","DOIUrl":"10.1016/j.jaci.2025.05.032","url":null,"abstract":"<div><h3>Background</h3><div>Component-resolved diagnostics allow detailed assessment of IgE sensitization to multiple allergenic molecules (component-specific IgEs, or c-sIgEs) and may be useful for asthma diagnosis. However, to effectively use component-resolved diagnostics across diverse settings, it is crucial to account for geographic differences.</div></div><div><h3>Objective</h3><div>We investigated spatial determinants of c-sIgE networks to facilitate development of diagnostic algorithms applicable globally.</div></div><div><h3>Methods</h3><div>We used multiplex component-resolved diagnostics array to measure c-sIgE to 112 proteins in an international collaboration of several studies: WASP (World Asthma Phenotypes; United Kingdom, New Zealand, Brazil, Ecuador, and Uganda), U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes; 7 European countries), and MAAS (Manchester Asthma and Allergy Study, a UK population-based birth cohort). Hierarchical clustering on low-dimensional representation of co-occurrence networks ascertained sensitization and c-sigE clusters across populations. Cross-country comparisons focused on a common subset of 18 c-sIgEs. We investigated sensitization networks across regions in relation to asthma severity.</div></div><div><h3>Results</h3><div>Sensitization profiles shared similarities across regions. For 18 c-sIgEs shared across study populations, the response structure enabled differentiation between different geographic areas and study designs, revealing 3 clusters: (1) Uganda, Ecuador, and Brazil, (2) U-BIOPRED children and adults, and (3) New Zealand, United Kingdom, and MAAS. Spectral clustering identified differences between clusters. We observed constant, almost parallel shifts between severe and nonsevere asthma in each country.</div></div><div><h3>Conclusions</h3><div>Patterns of c-sIgE response reflect geographic location and study design. However, despite geographic differences in c-sIgE networks, there is a remarkably consistent shift between networks of subjects with nonsevere and severe asthma.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 262-272"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547689","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":"Prediction and characterization of genetically regulated expression of asthma tissues from African-ancestry populations","authors":"Sarah D. Slack BS ,&nbsp;Erika Esquinca MS ,&nbsp;Christopher H. Arehart BS ,&nbsp;Meher Preethi Boorgula MS ,&nbsp;Brooke Szczesny MS ,&nbsp;Alex Romero MS ,&nbsp;Monica Campbell MS ,&nbsp;Sameer Chavan MS ,&nbsp;Nicholas Rafaels MS ,&nbsp;Harold Watson MD ,&nbsp;R. Clive Landis PhD ,&nbsp;Nadia N. Hansel MD, MPH ,&nbsp;Charles N. Rotimi PhD ,&nbsp;Christopher O. Olopade MD, MPH ,&nbsp;Camila A. Figueiredo PhD ,&nbsp;Carole Ober PhD ,&nbsp;Andrew H. Liu MD ,&nbsp;Eimear E. Kenny PhD ,&nbsp;Kai Kammers PhD ,&nbsp;Ingo Ruczinski PhD ,&nbsp;Randi K. Johnson PhD, MPH","doi":"10.1016/j.jaci.2025.07.035","DOIUrl":"10.1016/j.jaci.2025.07.035","url":null,"abstract":"<div><h3>Background</h3><div>Genetic control of gene expression in asthma-related tissues is not well characterized, particularly for African-ancestry populations, limiting advancement in our understanding of the increased prevalence and severity of asthma in these populations.</div></div><div><h3>Objective</h3><div>We sought to create novel transcriptome prediction models for asthma tissues (nasal epithelium and CD4⁺ T cells) and apply them in a transcriptome-wide association study (TWAS) to discover candidate asthma genes.</div></div><div><h3>Methods</h3><div>We developed and validated gene expression prediction databases for unstimulated CD4⁺ T cells and nasal epithelium using an elastic net framework. Combining these with existing prediction databases (N = 51), we performed a TWAS of 9284 individuals of African ancestry to identify tissue-specific and cross-tissue candidate genes for asthma.</div></div><div><h3>Results</h3><div>Novel databases for CD4⁺ T cells and nasal epithelial gene expression prediction contain 8,351 and 10,296 genes, respectively, including 4 asthma loci (<em>SCGB1A1</em>, <em>MUC5AC</em>, <em>ZNF366</em>, and <em>LTC4S</em>) not predictable with existing public databases. Prediction performance was comparable to existing databases and was most accurate for populations sharing ancestry with the training set (eg, African ancestry). From the TWAS, we identified 17 candidate causal asthma genes (adjusted <em>P</em> &lt; .1), including genes with tissue-specific (<em>IL33</em> in nasal epithelium) and cross-tissue (<em>CCNC</em> and <em>FBXW7</em>) effects.</div></div><div><h3>Conclusions</h3><div>Expression of <em>IL33</em>, <em>CCNC</em>, and <em>FBXW7</em> may affect asthma risk in African- ancestry populations by mediating inflammatory responses. The addition of CD4⁺ T cell and nasal epithelium prediction databases to the public sphere will improve ancestry representation and power to detect novel gene-trait associations from TWAS.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 253-261"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031962","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":"Caspase 1–deficient humans survive into late adulthood despite dramatically lower canonical inflammasome activity","authors":"John Dominy PhD ,&nbsp;Christopher Koch MS ,&nbsp;Christelle Arnold MS ,&nbsp;Vinney George MS ,&nbsp;Maleeha Zaman Khan MS ,&nbsp;Shareef Khalid MS ,&nbsp;Aneeqa Bano MS ,&nbsp;Muhammad Rehan Mian MSPH ,&nbsp;Wafa Gul MBBS ,&nbsp;Muhammad Bilal Liaqat MS ,&nbsp;Lubna Kamani FRCP ,&nbsp;Nazish Butt FCPS ,&nbsp;Marium Dahar MS ,&nbsp;Namra Saqib MS ,&nbsp;Anjum Jalal FRCS ,&nbsp;Shahid Abbas FCPS ,&nbsp;Riffat Sultana FCPS ,&nbsp;Musfireh Siddiqeh FCPS, FACS ,&nbsp;Syed Shahzaib Raza MCS ,&nbsp;Muhammad Haroon FACR, PhD ,&nbsp;Danish Saleheen MBBS, PhD","doi":"10.1016/j.jaci.2025.09.025","DOIUrl":"10.1016/j.jaci.2025.09.025","url":null,"abstract":"<div><h3>Background</h3><div>Caspase-1 (CASP1) is a key effector of the canonical inflammasome and innate immunity. Inhibitors of the canonical inflammasome pathway are in clinical development for multiple inflammatory pathologies, but efficacy and long-term safety effects of these molecules are yet to be established. Complete CASP1 deficiency in humans, which has not been described, would yield valuable insights for therapeutic inhibitor development and fundamental immunobiology.</div></div><div><h3>Objective</h3><div>We sought to identify and characterize individuals with ultrarare, homozygous loss-of-function variants in CASP1 using a large consanguineous biobank, the Pakistan Genome Resource, and recall-by-genotype studies.</div></div><div><h3>Methods</h3><div>Homozygotes of a loss-of-function CASP1 variant (Tyr153Ter) were recontacted and, along with consenting family members, clinically profiled for a wide range of phenotypes.</div></div><div><h3>Results</h3><div>Eight homozygotes of Tyr153Ter, 19 heterozygotes of Tyr153Ter, and 17 homozygotes of the reference allele are described in 2 separate families. Complete CASP1 deficiency is associated with near-absence of IL-18 and lower white blood cell counts. IL-1β secretion is absent in stimulated CASP1-deficient PBMCs but is detectable at low levels in circulation, suggesting alternative IL-1β processing pathways in humans. CASP1-deficient humans have survived into advanced age and have children, both without an overt increase in infection risk.</div></div><div><h3>Conclusions</h3><div>Complete loss of CASP1 in humans dramatically reduces activity of the canonical inflammasome but does not overtly increase risk of infection observations or radically affect human reproduction and development through to late adulthood. These findings establish safety and biomarker data for ongoing clinical programs.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 217-225"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305592","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":"CME Calendar-AAAAI","authors":"","doi":"10.1016/S0091-6749(25)01153-4","DOIUrl":"10.1016/S0091-6749(25)01153-4","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages A21-A22"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895815","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 role of CC16 in the associations of preterm birth with lung function and asthma in adult life","authors":"Nipasiri Voraphani MD ,&nbsp;Susanna Klevebro MD, PhD ,&nbsp;Fredrik Larsson MD ,&nbsp;Gang Wang MD, PhD ,&nbsp;Simon Kebede Merid PhD ,&nbsp;Sophia Björkander PhD ,&nbsp;Petra Um-Bergström MD, PhD ,&nbsp;Anna Bergström PhD ,&nbsp;Inger Kull PhD ,&nbsp;Anne-Sophie Merritt PhD ,&nbsp;Amber L. Spangenberg BS ,&nbsp;Tara F. Carr MD ,&nbsp;Debra A. Stern MS ,&nbsp;Julie G. Ledford PhD ,&nbsp;Brian R. Hallmark PhD ,&nbsp;Erik Melén MD, PhD ,&nbsp;Stefano Guerra MD, PhD","doi":"10.1016/j.jaci.2025.09.004","DOIUrl":"10.1016/j.jaci.2025.09.004","url":null,"abstract":"<div><h3>Background</h3><div>Club cell secretory protein (CC16) is a pneumoprotein that has anti-inflammatory and antimicrobial properties and whose levels are reduced in preterm infants.</div></div><div><h3>Objective</h3><div>We sought to investigate the role of circulating CC16 in the association of preterm birth (&lt;37 weeks) with lung function and asthma from childhood into young adult life in longitudinal and mediation analyses.</div></div><div><h3>Methods</h3><div>Using the BAMSE (Swedish abbreviation for Barn/Children, Allergy, Milieu, Stockholm, Epidemiology) birth cohort (2,557 participants and 10,631 longitudinal observations), we assessed plasma CC16 (ages 8 and 24 years), spirometry (ages 8, 16, 24, and 26 years), and asthma (ages 8, 12, 16, 24, and 26 years). Longitudinal associations between preterm birth, CC16, percent predicted values of FEV₁/forced vital capacity (ppFEV₁/FVC), and asthma were examined in longitudinal multivariable mixed models. CC16 (ages 8-24 years) was tested as a mediator for the relationship of preterm birth to pre- and postbronchodilator ppFEV₁/FVC and asthma in adulthood (ages 24-26 years).</div></div><div><h3>Results</h3><div>Preterm birth was associated with reduced plasma CC16 (−1.15 ng/mL; 95% CI, −1.22 to −1.08; <em>P</em> &lt; .0001), lower ppFEV₁/FVC (−1.9%; 95% CI, −3.1 to −0.8; <em>P</em> = .001), and higher risk for asthma (1.83; 95% CI, 1.28 to 2.62; <em>P</em> = .001) across ages 8 to 26 years. CC16 deficits were related to decreased ppFEV₁/FVC (<em>P</em> &lt; .0001) and increased risk for asthma (<em>P</em> = .007) in adulthood. Multivariable mediation analyses suggested that CC16 mediated 16% and 9% of the effects of preterm birth on ppFEV₁/FVC and asthma in adult life, respectively.</div></div><div><h3>Conclusions</h3><div>Low CC16 is a potential mediator of the effects of prematurity on lung function deficits and asthma in young adulthood. Future studies should address whether CC16 can be used as a predictive biomarker and, possibly, a therapeutic target in individuals born preterm.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 89-98"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103284","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":"Guideline adherence to aeroallergen-focused activities in adult asthma care: Insights from an online survey","authors":"Patrick K. Gleeson MD, MSCE ,&nbsp;Knashawn H. Morales ScD ,&nbsp;Hannah J. Lee MD ,&nbsp;Olajumoke O. Fadugba MD ,&nbsp;Priya J. Patel MD ,&nbsp;Audreesh Banerjee MD ,&nbsp;Andrea J. Apter MD, MSc, MA ,&nbsp;Jason D. Christie MD, MSCE ,&nbsp;Meeta Prasad Kerlin MD, MSCE","doi":"10.1016/j.jaci.2025.09.013","DOIUrl":"10.1016/j.jaci.2025.09.013","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 280-282"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261306","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":"Human milk oligosaccharides and polyphenols: Mechanisms, effects, and applications in allergies","authors":"Chantal C.M. den Elzen MSc ,&nbsp;Ariana Carvalho MSc ,&nbsp;Stanislawa Bazan-Socha MD, PhD ,&nbsp;Prescilla V. Jeurink PhD ,&nbsp;Malgorzata Wygrecka PhD ,&nbsp;Mirjam Kool PhD ,&nbsp;Johan Garssen MD, PhD ,&nbsp;Daniel P. Potaczek MD, PhD ,&nbsp;Holger Garn PhD ,&nbsp;Betty C.A.M. van Esch PhD","doi":"10.1016/j.jaci.2025.09.029","DOIUrl":"10.1016/j.jaci.2025.09.029","url":null,"abstract":"<div><div>Human milk offers the best nutrition to the infant, which is crucial for the child’s proper development and health status across the lifespan. Besides providing the substances optimally supplying the baby with energy and building materials, breast milk contains several immunometabolically active components. Those include molecules fully <em>de novo</em> synthesized by the mother, such as human milk oligosaccharides (HMO), and substances of nonhuman origin, transferred to the infant through mother’s milk, such as dietary plant polyphenols. In this review, we outline the basic biology of HMO and polyphenols and deeply characterize their effects on the development of allergic disorders on the basis of available literature reporting data from <em>in vitro,</em> animal, and human studies. Further, we review the abundance of HMO and polyphenols, commonly present in mother’s milk, and their mutual interactions in the context of the mechanisms underlying predisposition to, or protection against, the development of allergies. Finally, we discuss the potential of HMO and polyphenols in allergy prevention and therapy.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 18-37"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357688","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 Editors’ Choice","authors":"","doi":"10.1016/j.jaci.2025.11.006","DOIUrl":"10.1016/j.jaci.2025.11.006","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 62-67"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895925","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":"Traffic-emitted ultrafine particles disrupt macrophage efferocytosis and resolution of allergic lung inflammation","authors":"Thayse R. Brüggemann PhD ,&nbsp;Luciana P. Tavares PhD ,&nbsp;Nicole Almanzar BS ,&nbsp;Dilpreet Singh ScD ,&nbsp;Holly Batchelder BA ,&nbsp;Robert Nshimiyimana PhD ,&nbsp;Adam L. Haber PhD ,&nbsp;Philip Demokritou PhD ,&nbsp;Charles N. Serhan PhD, DSc ,&nbsp;Bruce D. Levy MD","doi":"10.1016/j.jaci.2025.08.014","DOIUrl":"10.1016/j.jaci.2025.08.014","url":null,"abstract":"<div><h3>Background</h3><div>Particulate matter (PM) in air pollution is a major health concern. PM includes ultrafine particles (UFPs; PM_0.1 and particles of ≤0.1 μm), which can evoke lung inflammation. However, the impact of UFPs on the resolution of lung inflammation, a potentially important link to chronic inflammatory diseases, remains to be determined.</div></div><div><h3>Objective</h3><div>We sought to investigate the impact of UFPs on the resolution of allergic lung inflammation and to identify potential therapeutic interventions to mitigate these effects.</div></div><div><h3>Methods</h3><div>UFPs were collected from urban Boston. Using a mouse model, transient allergic lung inflammation was induced by exposure to house dust mite. Mice were then exposed to UFPs, and their inflammatory responses were assessed. The therapeutic potential of a resolution agonist, resolvin D2 (RvD2; 7<em>S</em>,16<em>R</em>,17<em>S</em>-trihydroxy-4<em>Z</em>,8<em>E</em>,10<em>Z</em>,12<em>E</em>,14<em>E</em>,19<em>Z</em>-docosahexaenoic acid), was also determined.</div></div><div><h3>Results</h3><div>UFP exposure impaired lung eosinophil clearance and reduced macrophage efferocytosis, key processes in resolving lung inflammation. This disruption was mediated by altered expression of ecto-5′-nucleotidase (<em>Nt5e</em>, gene encoding for CD73). Administration of RvD2, a potent proresolving mediator, increased macrophage efferocytosis of apoptotic eosinophils and neutrophils and partially corrected the UFP-disrupted resolution mechanisms.</div></div><div><h3>Conclusions</h3><div>Environmental exposure to traffic-emitted UFPs can fundamentally undermine endogenous resolution processes—pathologic mechanisms that can be partially rescued by signaling pathways activated by RvD2.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 238-252"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962744","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":"Epithelial cell derived lumican modulates extracellular matrix dynamics in early-life airways disease","authors":"Franz Puttur PhD ,&nbsp;William J. Traves MSc ,&nbsp;Minerva G. Martin MSc ,&nbsp;Samuele Di Carmine MSc ,&nbsp;Frédéric Fercoq PhD ,&nbsp;David C.A. Gaboriau PhD ,&nbsp;Lewis J. Entwistle PhD ,&nbsp;Laura Yates PhD ,&nbsp;Régis Joulia PhD ,&nbsp;Sara Patti MSc ,&nbsp;Helen Stölting PhD ,&nbsp;Ciara Campbell MSc ,&nbsp;Mindy L. Gore PhD ,&nbsp;Simone A. Walker MSc ,&nbsp;Lola E. Loewenthal MD ,&nbsp;Philip L. Molyneaux MD ,&nbsp;Leo M. Carlin PhD ,&nbsp;Sejal Saglani MD ,&nbsp;Clare M. Lloyd PhD","doi":"10.1016/j.jaci.2025.08.030","DOIUrl":"10.1016/j.jaci.2025.08.030","url":null,"abstract":"<div><h3>Background</h3><div>Airway remodeling is a prominent pathologic feature in preschool wheeze (PSW) and school-age asthma (SA). Although the relationships between altered lung function, extracellular matrix (ECM) changes, and airway remodeling are described in PSW and SA, the underlying mechanisms remain undefined.</div></div><div><h3>Objective</h3><div>We sought to investigate mechanisms resulting in altered airway ECM landscape in PSW (1-5 years of age) and SA (6-16 years of age) and track ECM dynamics in house dust mite (HDM)–exposed neonatal mice.</div></div><div><h3>Methods</h3><div>We applied spatial transcriptomics, confocal microscopy, and SHG microscopy in PSW and SA endobronchial biopsy specimens and in HDM-exposed neonatal mice lung specimens to reveal transcriptional, phenotypic, and structural ECM–associated changes during allergic airway inflammation.</div></div><div><h3>Results</h3><div>Spatial transcriptomic analysis of the airways of children with PSW and SA revealed increased gene expression for fibrillar collagens I, II, and III and basement membrane collagen VI in fibroblast-rich regions in both diseases. Similarly, increased collagen III and collagen VI deposition with exaggerated collagen fibril disorganization was observed in the peribronchial regions of HDM-exposed neonatal mice. Collagen disorganization was also evident in the airways of children with PSW and SA and was accompanied by increased production of bronchial epithelial cell–derived lumican and increased airway lumican in children with PSW, children with SA, and HDM-exposed neonatal mice. Lumican directly altered primary healthy airway fibroblast function, increasing proliferation and collagen production.</div></div><div><h3>Conclusions</h3><div>We demonstrate a previously uncharacterized role of collagen-associated phenotypic and geometric changes in early-life airway remodeling and show lumican as a crucial remodeling factor associated with collagen organization in PSW and SA.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 1","pages":"Pages 176-189"},"PeriodicalIF":11.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089755","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}