Journal of Allergy and Clinical Immunology最新文献

{"title":"News beyond our pages","authors":"","doi":"10.1016/j.jaci.2025.08.006","DOIUrl":"10.1016/j.jaci.2025.08.006","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 904-905"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204514","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":"Positionally distinct interferon-stimulated dermal immune-acting fibroblasts promote neutrophil recruitment in Sweet syndrome","authors":"Kellen J. Cavagnero PhD ,&nbsp;Julie Albright BS ,&nbsp;Fengwu Li PhD ,&nbsp;Edward Liu ,&nbsp;Tatsuya Dokoshi MD, PhD ,&nbsp;Rachael Bogle MS ,&nbsp;Joseph Kirma BS ,&nbsp;J. Michelle Kahlenberg MD, PhD ,&nbsp;Allison C. Billi MD, PhD ,&nbsp;Jennifer Fox BS ,&nbsp;May P. Chan MD ,&nbsp;Anthony Coon ,&nbsp;Craig J. Dobry ,&nbsp;Brian Hinds MD ,&nbsp;Lam C. Tsoi PhD ,&nbsp;Paul W. Harms MD, PhD ,&nbsp;Johann E. Gudjonsson MD, PhD ,&nbsp;Richard L. Gallo MD, PhD","doi":"10.1016/j.jaci.2025.05.029","DOIUrl":"10.1016/j.jaci.2025.05.029","url":null,"abstract":"<div><h3>Background</h3><div>Sweet syndrome is an inflammatory skin disease characterized by robust neutrophil infiltration into the dermis. The pathogenesis of Sweet syndrome and its distinguishing features compared to other neutrophilic dermatoses, such as pyoderma gangrenosum, remain poorly understood.</div></div><div><h3>Objective</h3><div>Our aim was to define the cellular and molecular landscape of the skin of patients with Sweet syndrome.</div></div><div><h3>Methods</h3><div>Single-nucleus and bulk transcriptomics were performed on archival clinical skin samples from patients with Sweet syndrome, patients with pyoderma gangrenosum, and healthy controls. For mechanistic validation, functional experiments were performed with primary human cells. Spatial transcriptomics with single-molecule resolution was used to map cell types to tissue location.</div></div><div><h3>Results</h3><div>A prominent interferon signature was identified in Sweet syndrome skin that was reduced in tissue samples from patients with pyoderma gangrenosum and healthy controls. This signature was observed in different subsets of cells, including fibroblasts that expressed interferon-induced genes. Functionally, this response was supported by analysis of cultured dermal fibroblasts that were observed to highly express neutrophil chemokines in response to activation by type I interferon. Furthermore, spatial transcriptomics revealed 2 positionally distinct interferon-activated fibroblast subsets: CXCL1-positive fibroblasts near neutrophil infiltrates and CXCL12-positive fibroblasts distal to these infiltrates.</div></div><div><h3>Conclusion</h3><div>This study defines the cellular and molecular landscape of neutrophilic dermatoses and implicates dermal immune-acting fibroblasts in Sweet syndrome pathogenesis through type I interferon recognition and neutrophil recruitment.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 966-979.e8"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293772","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":"Mouse TH2 cell extracellular vesicles promote eosinophil survival through the surface cytokine cargo IL-3","authors":"Kaitlyn E. Bunn MS ,&nbsp;Brenna G. Giese-Byrne BS ,&nbsp;Alexander M. Blatt BA ,&nbsp;Dawn C. Newcomb PhD ,&nbsp;Heather H. Pua MD, PhD","doi":"10.1016/j.jaci.2025.05.027","DOIUrl":"10.1016/j.jaci.2025.05.027","url":null,"abstract":"<div><h3>Background</h3><div>Extracellular vesicles (EVs) mediate intercellular communication during immune responses. EVs are abundant in respiratory biofluids, and the composition of EVs in the lung changes during inflammation.</div></div><div><h3>Objective</h3><div>We sought to quantify the contribution of T cells to airway EVs in eosinophilic lung inflammation and ascertain their function during a type 2 inflammatory response.</div></div><div><h3>Methods</h3><div>Genetic membrane tagging was combined with single vesicle flow cytometry to quantify T-cell EVs in the airways of mice challenged with ovalbumin or house dust mite. EVs were purified from mouse T_H2 cell cultures, and their functions on eosinophils were assessed by flow cytometry and RNA sequencing. T_H2 cell EVs were instilled into the lungs of mice to determine effects on lung eosinophilia. Finally, the function of an EV protein cargo was tested using inhibitors and blocking antibodies.</div></div><div><h3>Results</h3><div>T-cell EVs are increased in the airways of mice after ovalbumin- or house dust mite–induced inflammation. EVs secreted by T_H2 cells inhibit apoptosis and induce activating pathways in eosinophils <em>in vitro.</em> This effect depends on restimulation through the T-cell receptor. T_H2 cell EVs prolong eosinophilia <em>in vivo</em> during acute eosinophilic inflammation. T_H2 cell EVs carry the cytokine IL-3 as a surface cargo, which inhibits apoptosis by activating JAK1/2-dependent pro-survival programs in eosinophils.</div></div><div><h3>Conclusions</h3><div>T_H2 cell EVs promote eosinophil survival through the EV cargo IL-3, supporting a role for EVs as vehicles of cytokine-based communication in lung inflammation.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 1053-1065"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284434","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":"Opsin 3 in keratinocytes mediates the light-induced exaggeration of atopic dermatitis","authors":"Liya Mao MD ,&nbsp;Huibin Yin MD, PhD ,&nbsp;Zhuoqiong Qiu MD, PhD ,&nbsp;Lingjie Zhao MD ,&nbsp;Shangshang Wang MD, PhD ,&nbsp;Yu Wang MD, PhD ,&nbsp;Yuemeng Wu MD, PhD ,&nbsp;Chaoying Gu MD, PhD ,&nbsp;Xu Yao MD, PhD ,&nbsp;Wei Li MD, PhD","doi":"10.1016/j.jaci.2025.05.015","DOIUrl":"10.1016/j.jaci.2025.05.015","url":null,"abstract":"<div><h3>Background</h3><div>Atopic dermatitis (AD) is a common chronic inflammatory skin disease often exaggerated by sun exposure, whereas sun-exposed regions are usually spared from psoriasis. Opsin 3 (OPN3), a photoreceptor, has been implicated in nonvisual functions of the skin including skin pigmentation and barrier restoration. However, whether OPN3 engages in light-induced inflammation of AD remains unclear.</div></div><div><h3>Objective</h3><div>We sought to explore the role and mechanism of OPN3 in light-induced exaggeration of AD.</div></div><div><h3>Methods</h3><div>The expression of OPN3 was assessed by reverse transcription quantitative PCR, western blotting, immunohistochemistry, and immunofluorescence. The roles of light and OPN3 in type 2 inflammation were evaluated in mouse models and cultured keratinocytes (KCs). The mechanisms by which OPN3 regulates light-induced inflammation in KCs were examined by bulk RNA-sequencing, ELISA, calcium imaging, and immunofluorescence.</div></div><div><h3>Results</h3><div>We found that OPN3 expression was increased in KCs of skin lesion from patients with AD and MC903-induced AD mouse model, but not patients with psoriasis or imiquimod-induced psoriasis mouse model. Type 2 cytokines induced OPN3 expression in KCs, which upregulated the production of proinflammatory cytokine IL-36γ, TNF-α, IL-8, and IL-1β. Notably, light exposure exaggerated skin inflammation in mouse model of AD, but not psoriasis. Moreover, light triggered the production of proinflammatory cytokines in KCs through OPN3-mediated calcium influx and sphingosine 1-phosphate-sphingosine 1-phosphate receptor signaling.</div></div><div><h3>Conclusion</h3><div>OPN3 plays a microenvironment-specific proinflammatory role in KCs upon light exposure, and may serve as a candidate of therapeutic targets for AD.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 980-992"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199185","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":"Genetic risk for adult obstructive lung function and its early life associations","authors":"Casper-Emil T. Pedersen PhD ,&nbsp;Anders Eliasen PhD ,&nbsp;Kasper Fischer-Rasmussen PhD ,&nbsp;Yang Luo PhD ,&nbsp;Frederikke Skov MD ,&nbsp;Astrid Sevelsted PhD ,&nbsp;Jonathan Thorsen MD, PhD ,&nbsp;Jens-Ulrik Stæhr Jensen MD ,&nbsp;Jørgen Vestbo MD ,&nbsp;Thomas Werge PhD ,&nbsp;Andreanne Morin PhD ,&nbsp;Carole Ober PhD ,&nbsp;Morten A. Rasmussen PhD ,&nbsp;George Davey Smith MD, DSc, FRS ,&nbsp;Jakob Stokholm MD, PhD ,&nbsp;Bo Chawes MD, PhD, DMSc ,&nbsp;Klaus Bønnelykke MD, PhD","doi":"10.1016/j.jaci.2025.06.035","DOIUrl":"10.1016/j.jaci.2025.06.035","url":null,"abstract":"<div><h3>Background</h3><div>Chronic obstructive pulmonary disease may partly originate in early life under influence from prenatal or early postnatal risk factors, including genetic predisposition.</div></div><div><h3>Objectives</h3><div>We investigated the extent to which the genetic predisposition to adult obstructive lung function manifests already at birth and throughout childhood in terms of impaired lung function, bronchial responsiveness, and asthma-related symptoms.</div></div><div><h3>Methods</h3><div>We constructed a polygenic risk score (PRS) for adult obstructive lung function (FEV₁/forced vital capacity [FVC]) and associated it with neonatal and childhood lung function, bronchial responsiveness, asthma, and respiratory tract infections in the COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) birth cohorts, and with hospitalization for wheeze, asthma, and infections in 114,283 unrelated individuals from the The Lundbeck Foundation Initiative for Integrative Psychiactric Research (iPSYCH) cohort.</div></div><div><h3>Results</h3><div>The FEV₁/FVC PRS was associated with obstructive lung function shortly after birth (eg, neonatal FEV_0.5/FVC [β: −0.20; 95% CI: −0.31 to −0.09; <em>P</em> &lt; .0003]), with continued progression into adolescence. A higher PRS was also linked to an increased risk of severe wheeze/asthma episodes (odds ratio: 1.24; 95% CI: 1.19-1.29; <em>P</em> = 1.6 × 10⁻²⁶) and lower respiratory tract infections (odds ratio: 1.09; 95% CI: 1.06-1.12; <em>P</em> = 3.5 × 10⁻⁸) requiring hospitalization, which was evident a few months after birth. In COPSAC₂₀₀₀, there was no evidence of asthma exacerbations mediating the association between FEV₁/FVC PRS and lung function by age 18 years.</div></div><div><h3>Conclusions</h3><div>Genetic predisposition to obstructive lung function was evident shortly after birth in terms of impaired neonatal lung function and increased susceptibility to severe wheeze, asthma, and lower respiratory tract infections. This indicates prenatal life and early childhood as a window of opportunity for improving lung health in adulthood.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 937-947"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701341","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)00908-X","DOIUrl":"10.1016/S0091-6749(25)00908-X","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages A23-A24"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204512","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":"STING stimulates recruitment of inflammatory cells and airway fibrosis in chronic allergic airway inflammation","authors":"Koa Hosoki PhD,&nbsp;Annamalai Govindhan PhD,&nbsp;Sanjiv Sur MD","doi":"10.1016/j.jaci.2025.06.020","DOIUrl":"10.1016/j.jaci.2025.06.020","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 1120-1123"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640202","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":"Single-cell transcriptomic profiling of eosinophils and airway immune cells in childhood asthma","authors":"Naresh Doni Jayavelu PhD ,&nbsp;Andrew H. Liu MD ,&nbsp;Courtney Gaberino MD ,&nbsp;Kristy Freeman MBS ,&nbsp;Matthew Lawrance MS ,&nbsp;Stephan Pribitzer PhD ,&nbsp;Clara Seifert BS ,&nbsp;Cullen Dutmer MD ,&nbsp;Alkis Togias MD ,&nbsp;Patrice M. Becker MD ,&nbsp;William W. Busse MD ,&nbsp;Christine A. Sorkness PharmD ,&nbsp;Carmen Mikacenic MD ,&nbsp;Kimberly A. Dill-McFarland PhD ,&nbsp;Daniel J. Jackson MD ,&nbsp;Matthew C. Altman MD","doi":"10.1016/j.jaci.2025.06.034","DOIUrl":"10.1016/j.jaci.2025.06.034","url":null,"abstract":"<div><h3>Background</h3><div>Single-cell RNA sequencing has transformed our understanding of cellular heterogeneity but remains inadequate in capturing granulocytes, particularly in tissue compartments, owing to technical limitations.</div></div><div><h3>Objective</h3><div>To enhance granulocyte recovery in single-cell RNA sequencing, we used nasal lavage samples from children with asthma, leveraging the 10× Genomics Flex platform combined with a customized data processing pipeline.</div></div><div><h3>Methods</h3><div>Nasal lavage samples were processed without prior manipulation to avoid technical artifacts such as lysis or stimulation. Granulocyte recovery was optimized by using fixation to preserve cell quality and advanced computational techniques to separate cells with a low RNA content from background noise. Cell-type proportions were validated against histologic and bulk RNA data.</div></div><div><h3>Results</h3><div>The optimized approach achieved more than a16-fold increase in eosinophil detection versus in standard methods. This method successfully captured eosinophils, neutrophils, and other major cell types in proportions consistent with histologic and bulk RNA assessments, with no biased loss of cell types. Phenotypic comparisons between children with high-eosinophil and low-eosinophil asthma uncovered significant transcriptional differences, cell composition, and distinct biologic pathways in granulocytes, immune cells, and epithelial cells. Additionally, distinct subpopulations of eosinophils and neutrophils with unique functional profiles were identified; the identified subpopulations were uniquely associated with high- and low-eosinophil asthma phenotypes, highlighting the complexity of airway granulocyte inflammation.</div></div><div><h3>Conclusions</h3><div>This study provides a framework for efficient capture of granulocytes in tissue compartments, overcoming traditional limitations. The resulting data set serves as a valuable resource for understanding airway granulocyte biology and inflammation, enabling detailed exploration of asthma pathogenesis. Furthermore, this approach facilitates large-scale, multicenter translational studies and advances personalized therapeutic strategies for airway diseases.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 923-936"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669575","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":"Information for Readers","authors":"","doi":"10.1016/S0091-6749(25)00906-6","DOIUrl":"10.1016/S0091-6749(25)00906-6","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Page A19"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204510","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":"Current perspectives and challenges of using artificial intelligence in immunodeficiencies","authors":"Jacques G. Rivière MD, MSc ,&nbsp;Roser Cantenys-Saba MSc ,&nbsp;Gerard Carot-Sans PhD ,&nbsp;Jordi Piera-Jiménez PhD ,&nbsp;Manish J. Butte MD, PhD ,&nbsp;Pere Soler-Palacín MD, PhD ,&nbsp;Xiao P. Peng MD, PhD","doi":"10.1016/j.jaci.2025.06.015","DOIUrl":"10.1016/j.jaci.2025.06.015","url":null,"abstract":"<div><div>The rapid growth of artificial intelligence (AI) in health care is promising for screening and early diagnosis in settings that heavily rely on professional expertise, such as rare diseases like inborn errors of immunity (IEI). However, the development of AI algorithms for IEI and other rare diseases faces important challenges such as dataset sizes, availability and harmonization. Similarly, the implementation of AI-based strategies for screening and diagnosis of IEI in real-world scenarios is hampered by multiple factors including stakeholders’ acceptance, ethical and legal constraints, and technologic barriers. Consequently, while the body of literature on AI-based solutions for early diagnosis of IEI continues to expand, clinical utility and widespread implementation remain limited. In this review, we provide an up-to-date comprehensive review of current applications and challenges facing AI use for IEI diagnosis and care.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 878-888"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521496","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}