Allergy最新文献

{"title":"Correction to “Basophil Activation Test is a Complementary Tool in the Diagnosis of Immediate Reactions to Platinum Salts and Taxanes”","authors":"","doi":"10.1111/all.16671","DOIUrl":"10.1111/all.16671","url":null,"abstract":"<p>G. Bogas, A. Ariza, P. Vázquez-Revuelta, et al. “Basophil Activation Test is a Complementary Tool in the Diagnosis of Immediate Reactions to Platinum Salts and Taxanes,” <i>Allergy</i> 80, no. 1 (2025): 271–286. https://doi.org/10.1111/all.16296.</p><p>We apologize for this mistake.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16671","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927921","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}

{"title":"Two-Year Turning Point With Dupilumab in CRSwNP: Control, Remission, and Tapering Dosage.","authors":"Eugenio De Corso, Claudio Montuori, Carlotta Pipolo, Ignazio La Mantia, Ernesto Pasquini, Angelo Ghidini, Veronica Seccia, Giancarlo Ottaviano, Elena Cantone, Giulia Dané, Massimiliano Garzaro, Gian Luca Fadda, Sara Torretta, Francesca Anastasi, Frank Rikki Mauritz Canevari, Fabio Pagella, Daniela Lucidi, Carlo Cavaliere, Giulio Pagliuca, Marianna Maffei, Francesco Bussu, Marco Corbò, Leandro Maria D Auria, Gabriele De Maio, Antonella Loperfido, Stefania Gallo, Giuseppe D Agostino, Diana Giannarelli, Jacopo Galli","doi":"10.1111/all.70032","DOIUrl":"https://doi.org/10.1111/all.70032","url":null,"abstract":"<p><strong>Background: </strong>Dupilumab is an effective treatment for severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Most real-life studies have been conducted on small patient cohorts for up to 1 year.</p><p><strong>Methods: </strong>This ambispective, multicentric, 2-year-long study evaluated dupilumab effectiveness (including treatment response, disease control, and remission) and safety in severe, uncontrolled CRSwNP patients from the DUPIREAL Italian study centers.</p><p><strong>Results: </strong>The study involved 926 patients. At 24 months, median nasal polyp score (NPS), nasal obstruction visual analogue scale (VAS), Sino-nasal Outcome Test-22 (SNOT-22), and olfaction improved from baseline (all p < 0.0001). Patients with NPS > 4, and/or SNOT-22 > 30, and/or Sniffin' Sticks Identification Test-16 (SSIT-16) < 12 at 12 months demonstrated improvements in these outcomes over the second year. Overall, 18.7% of patients extended the dupilumab interdose interval to every 4 weeks (q4w). Notably, 91.2% of patients were \"good-to-excellent\" responders based on EPOS/Euforea criteria. Given the absence of standardized definitions for disease control and remission, we proposed different sets of criteria reporting results from different scenarios. Remission analysis is clinically important as it helps define treatment success and long-term therapeutic goals. Most adverse events were mild-to-moderate; 2.4% of patients discontinued treatment due to safety concerns.</p><p><strong>Conclusions: </strong>This is the largest real-life study evaluating dupilumab in CRSwNP over 2 years. Dupilumab showed sustained effectiveness, with progressive improvements across all clinical outcomes. Dupilumab tapering did not compromise outcomes; treatment continuation allowed meaningful clinical benefits in late responders. Two-year rates of disease control and remission are clinically relevant, although standardized criteria to assess these outcomes are needed.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937077","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":"Molecular IgE Sensitization Profiling With Micro-Arrayed Allergen Molecules in Adult Patients With Asthma From the LEAD Cohort: A Precision Medicine Approach.","authors":"Huey-Jy Huang, Robab Breyer-Kohansal, Katarzyna Niespodziana, Charmaine J M Lim, Marie-Kathrin Breyer, Rudolf Valenta, Sylvia Hartl","doi":"10.1111/all.70017","DOIUrl":"https://doi.org/10.1111/all.70017","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic respiratory disease comprising different pheno- and endotypes. Diagnostic tools for the identification of allergic versus non-allergic asthma are needed for new precision medicine-based treatments.</p><p><strong>Objective: </strong>To determine IgE sensitization profiles to multiple micro-arrayed allergen molecules in adult patients with asthma in the Austrian LEAD (Lung, hEart, sociAl, boDy) cohort; to compare IgE- and non-IgE sensitized patients with asthma; and to define possible allergen-specific immunotherapy concepts for sensitized patients.</p><p><strong>Methods: </strong>Out of 893 patients with a history of asthma, patients with current asthma (n = 436) were analyzed for IgE sensitizations to 110 micro-arrayed molecules from airborne and food allergen sources and by skin prick testing (SPT) with 10 allergen extracts (English plantain, mugwort, ragweed, timothy grass, ash tree, mites, dog, cat, Alternaria alternata, and Fagales mix). Clinical asthma-related parameters were compared between patients with IgE sensitization to asthma allergen molecules and non-IgE sensitized patients with asthma.</p><p><strong>Results: </strong>IgE sensitization was detected in 73.2% of patients with asthma using 63 micro-arrayed respiratory allergens. The most recognized respiratory outdoor allergen molecules were Bet v 1 (32.8%) and Ole e 1 (23.2%) followed by grass pollen, ragweed, and mugwort allergens. Fel d 1 was the most frequently recognized respiratory indoor allergen molecule (42.7%) followed by house dust mite and dog allergen molecules. Micro-arrayed allergens allowed the identification of IgE reactivity profiles indicative of genuine sensitizations to different allergen sources. IgE-sensitized patients were significantly younger than non-IgE-sensitized patients with asthma (median age 44 versus 58 years). Patients sensitized to respiratory allergens showed significantly better lung function (FEV1, FVC and FEV/FVC) and less dyspnea but more allergic bronchitis than non-IgE-sensitized patients with asthma. More IgE-sensitized patients used antihistamines but fewer inhaled corticosteroids than non-IgE-sensitized patients with asthma. Interestingly, eosinophil counts were lower both in ICS-treated as well as untreated sensitized patients than in non-sensitized patients with asthma.</p><p><strong>Conclusion: </strong>Molecular allergy diagnosis allowed the detection of genuine IgE sensitizations in adult patients with asthma; enabling stratification for precision medicine-based forms of personalized treatments such as allergen-based immunotherapy (AIT) and/or administration of biological treatments in asthma.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937044","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":"From Disease Control to Disease Modification: The Atopic Dermatitis Disease Activity Index","authors":"Thomas Bieber, Laura Maintz, Ganesh E. Phad, Marie‐Charlotte Brüggen","doi":"10.1111/all.70036","DOIUrl":"https://doi.org/10.1111/all.70036","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"106 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919315","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":"Physiological Level of Eosinophils Is Essential for the Regeneration and Homeostasis of Murine Hematopoietic Stem Cells","authors":"Chao Zhang, Weiwei Yi, Zhehua Shao, Bingpeng Yao, Guoxiong Tian, Fei Li, Xufei Du, Yangmingzi Hu, Yanqi Guo, Tao Wu, Wen Li, Zhihua Chen, Zhenyu Ju, Songmin Ying","doi":"10.1111/all.70021","DOIUrl":"https://doi.org/10.1111/all.70021","url":null,"abstract":"BackgroundEosinophils play a crucial role in host defense and immunity, yet their regulatory functions within the hematopoietic homeostasis remain poorly understood. Our prior investigations revealed that pathologically elevated eosinophil levels in asthma not only disrupt bone marrow hematopoietic stem cell (HSC) quiescence but also establish a self‐reinforcing cycle of eosinophil lineage commitment. Here, we further investigate the critical role of physiologically steady‐state levels of eosinophils in maintaining HSC functions.MethodsUsing eosinophil lineage‐specific null (Eos‐null) mice, we established models of chemotherapy‐induced HSC regeneration and competitive bone marrow transplantation (cBMT) assay to evaluate the impact of eosinophil depletion on HSC regeneration and function. In vitro colony forming assay assessed HSC reconstitute capability, while bone marrow chimeric mice were established with wild‐type (WT) and eosinophil‐related transgenic mice to further elucidate the role of physiological levels of eosinophils. RNA‐seq and cytokine array analyses were utilized to investigate the potential protective mechanisms of eosinophils.ResultsCompared to WT controls, Eos‐null mice exhibited significantly impaired HSC regeneration, characterized by a diminished response to 5‐fluorouracil (5‐FU) and carboplatin treatment. Both long‐term HSCs (LT‐HSCs) and lineage<jats:sup>−</jats:sup>Sca‐1<jats:sup>+</jats:sup>c‐Kit<jats:sup>+</jats:sup> (LSK) demonstrated compromised reconstitution capacity in vivo and in vitro. HSCs from Eos‐null mice demonstrated elevated apoptosis under 5‐FU treatment, potentially due to the absence of eosinophil‐derived protective factors. Conversely, both chimeric mice and eosinophil incorporation within bone marrow transplantation systems significantly disrupted HSC homeostasis and function.ConclusionPhysiological eosinophil level is essential for maintaining HSC regeneration, reconstitution capacity, and homeostasis.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"12 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919188","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":"Microbial Sharing Between Siblings Supports Metabolic Functions Protective Against Allergy","authors":"Hannah Devotta,&nbsp;Aonghus Lavelle,&nbsp;Katri Korpela,&nbsp;Sadhbh Hurley,&nbsp;Emer Shannon,&nbsp;Nonhlanhla Lunjani,&nbsp;Anoop Ambikan,&nbsp;Ujjwal Neogi,&nbsp;Carina Venter,&nbsp;Jens Walter,&nbsp;Jonathan Hourihane,&nbsp;Liam O'Mahony","doi":"10.1111/all.70033","DOIUrl":"10.1111/all.70033","url":null,"abstract":"&lt;p&gt;The association between siblings and protection from atopic disorders was first described by Strachan in 1989 [&lt;span&gt;1&lt;/span&gt;], a finding that formed the basis of the “hygiene hypothesis”. Multiple studies have since supported the association between birth order and allergic sensitization, potentially mediated via microbial exposures [&lt;span&gt;2&lt;/span&gt;]. Microbe-host interactions during early life help establish long-term patterns of immune reactivity that influence the risk of immune-mediated diseases such as allergies. We hypothesized that sibling-associated changes in infant microbiome composition and functional potential may enhance immune regulatory programs that protect against allergies. To test this hypothesis, we compared metagenomic sequencing data from infants with or without siblings born during strict pandemic-enforced social distancing measures (CORAL study) [&lt;span&gt;3&lt;/span&gt;] and identified the sibling-associated microbes and gene families that correlated with protection from food allergen sensitization.&lt;/p&gt;&lt;p&gt;Birth mode, type of feeding, home location or type of dwelling, pet ownership, childcare arrangements, smoking in the home or use of antibiotics for infants with (&lt;i&gt;n&lt;/i&gt; = 187) or without (&lt;i&gt;n&lt;/i&gt; = 164) siblings were similar for both groups (Table S1). Of the infants with older siblings, 130 had one sibling, 41 had two siblings, and 16 had three siblings. Alpha diversity was not significantly different between infants with or without siblings (Figure S1), but beta diversity was significantly different at both 6 (&lt;i&gt;p&lt;/i&gt; = 0.002) and 12 (&lt;i&gt;p&lt;/i&gt; = 0.001) months of age (Figure 1a,b), associated with significant changes in relative abundance of specific taxa that remained significant following adjustments for breastfeeding, birth mode, and external environmental factors (Figure 1c,d and Table S2). The number of siblings did not significantly affect these associations. Non-spore-forming taxa such as &lt;i&gt;Bifidobacterium&lt;/i&gt; species were enriched in infants with siblings, suggesting that living with older siblings overcomes the spatial and temporal barriers usually associated with the transfer of non-spore-forming microbes.&lt;/p&gt;&lt;p&gt;The overall relative abundance of gene families was not significantly different at 6 months of age (&lt;i&gt;p&lt;/i&gt; = 0.108) but was significantly different at 12 months of age (&lt;i&gt;p&lt;/i&gt; = 0.006) for infants with siblings that remained significant (&lt;i&gt;p&lt;/i&gt; = 0.007) following adjustments for breastfeeding, birth mode, and external environmental factors (Figure S2). Of the 4018 gene families identified in more than 20% of 6-month-old infants, 534 were significantly associated with having siblings, and 5 gene families remained significant following adjustment (Table S3). Gene Set Enrichment Analysis (GSEA) identified one pathway that was significantly different between infants with or without siblings at 6 months (Figure S3). At 12 months of age, 1237 gene families were significantly associated with siblings fol","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":"2934-2937"},"PeriodicalIF":12.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919316","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}

{"title":"Molecular Signatures and Functional Pathways of Human Monocytes and Macrophages in Allergy: An EAACI AllergoOncology Scoping Review","authors":"Rodolfo Bianchini,&nbsp;Andrea Escolar-Peña,&nbsp;Vanda Pick,&nbsp;Aurélie Poli,&nbsp;Rebecca Adams,&nbsp;José Basilio,&nbsp;Luigi Cari,&nbsp;Jitesh Chauhan,&nbsp;Tomás Chivato,&nbsp;Leticia de las Vecillas,&nbsp;María Isabel Delgado-Dolset,&nbsp;Maria M. Escribese,&nbsp;Melanie Grandits,&nbsp;Heather J. Bax,&nbsp;Isabel Adoración Martín-Antoniano,&nbsp;Leticia Martín-Cruz,&nbsp;Hanna Mayerhofer,&nbsp;Alessandro Michelucci,&nbsp;Giuseppe Nocentini,&nbsp;Gabriel Osborn,&nbsp;Carmela Pablo-Torres,&nbsp;Oscar Palomares,&nbsp;Mariona Pascal,&nbsp;Urszula Radzikowska,&nbsp;Nataliya Rohr-Udilova,&nbsp;Milena Sokolowska,&nbsp;Christoph Bergmann,&nbsp;Erika Jensen-Jarolim,&nbsp;Sophia N. Karagiannis,&nbsp;Rocio Rebollido-Rios,&nbsp;Elena Izquierdo","doi":"10.1111/all.16672","DOIUrl":"10.1111/all.16672","url":null,"abstract":"<p>AllergoOncology explores the intersection of allergic diseases and cancer, focusing on shared immune mechanisms. While monocytes and macrophages are extensively studied in cancer, their roles in allergic diseases remain underexplored. To address this gap, we conducted a scoping review to systematically characterize the molecular landscape and related pathways of human monocytes and macrophages in allergy. An automated search of PubMed and Web of Science databases retrieved 4668 unique articles, which were manually curated based on predefined inclusion and exclusion criteria, yielding 138 eligible studies. From these, we identified 451 molecules associated with monocyte and macrophage responses across allergic disorders. Data analyses revealed a research bias towards blood-derived monocytes, underrepresentation of tissue-resident macrophages, and limited inclusion of miRNAs. Semantic similarity and pathway enrichment analyses highlighted a common molecular signature across major allergic disorders, with consistent enrichment in interleukin signaling and immune activation pathways. To enhance reproducibility and translational utility for researchers and clinicians, we developed <span>ALO•HA</span>, a web application for interactive data exploration. This overview of monocyte and macrophage molecular responses in human allergy underscores the need for integrative, human-focused approaches to better define their roles, and to guide future therapeutic strategies in allergic diseases and at the interface with oncology.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":"2710-2725"},"PeriodicalIF":12.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919135","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}

{"title":"Development and Characterisation of a New In Vitro Murine Mucosal Mast Cell Model","authors":"Louise Battut,&nbsp;Jasper Kamphuis,&nbsp;Nadine Serhan,&nbsp;Laurent Reber,&nbsp;Nicolas Cenac,&nbsp;Gilles Dietrich,&nbsp;Eric Espinosa","doi":"10.1111/all.70022","DOIUrl":"10.1111/all.70022","url":null,"abstract":"&lt;p&gt;Mouse mast cells (MCs) fall into two subpopulations with well-defined roles and characteristics: connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs) [&lt;span&gt;1, 2&lt;/span&gt;]. While in vitro models of CTMCs exist in humans and mice, a reliable and relevant model of MMCs is still lacking. While a few previously described protocols have used the addition of TGF-β1 and IL-9 alongside IL-3 and SCF from the onset of bone marrow cell culture to generate MMC-like cells, these approaches often vary in culture duration and in the nature of the resulting cells [&lt;span&gt;3, 4&lt;/span&gt;]. Here, we propose a two-step protocol that more faithfully reflects the two major stages of MMC differentiation, enabling the generation of mouse bone marrow-derived mucosal mast cells (BM-MMCs) in vitro. Bone marrow cells were cultured in a complete Opti-MEM medium supplemented with IL-3 and SCF for 4 weeks to induce MC commitment before adding for one additional week both IL-9 and TGF-β1 to promote MMC proliferation and maturation [&lt;span&gt;2, 3, 5&lt;/span&gt;] (Figures 1A and S1). This delayed addition of IL-9 and TGF-β1 resulted in a higher percentage of cells showing an MMC phenotype compared with its addition at the start of culture (Figure S2). BM-MMCs were phenotypically and functionally compared to the previously established CTMC model (PCMCs) [&lt;span&gt;6&lt;/span&gt;]. In 5 weeks, this two-step differentiation protocol produces approximately 35 million MCs (36 ± 9 million, &lt;i&gt;n&lt;/i&gt; = 7 mice) from 1 million bone marrow cells (Figure S3A). After 7 weeks in culture, the BM-MMC showed more than 95% viability (Figure S3B). BM-MMCs expressed the MC markers FcεRI, CD117 and ST2 (IL-33 receptor) together with the typical MMC markers CD103 and MCPT1 (Figure 1B–D) and showed IL-3 dependency (Figure S4). Furthermore, these cells did not stain positively for avidin (which binds to heparin contained in the granules of CTMCs) (Figure 1D) and exhibited a reduced granular mass, histamine, and MCPT6 contents as compared to their PCMC counterparts (Figure 1E–G). BM-MMCs degranulated in response to FcεRI aggregation but not to the 48/80 compound secretagogue, as expected for MMCs which do not express its receptor Mrgprb2 (Figure 1H–J).&lt;/p&gt;&lt;p&gt;Transcriptomic analysis showed clear differences in gene expression between the two cell types. Among the 40 most variable genes, the typical MMC genes &lt;i&gt;Mcpt1&lt;/i&gt;, &lt;i&gt;Mcpt2, Mcpt8 and Itgae&lt;/i&gt;, and the typical CTMC genes &lt;i&gt;Mrgprb2&lt;/i&gt; and &lt;i&gt;Mrgprb1&lt;/i&gt; were clearly clustered in BM-MMCs and PCMCs, respectively (Figure S5A). We found 5174 differentially expressed genes (DEGs, Padj &lt; 0.01 and Fold change &gt; 2) (Figure 2A and Table S1) between BM-MMCs and PCMCs. Further analysis of the expression of the prototypical MC genes substantiated that BM-MMCs displayed MMC features, including a diminished ability to produce histamine and the expression of genes involved in chondroitin sulfate synthesis (Figure 2B–D) (5). This analysis also revealed that recep","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":"2926-2930"},"PeriodicalIF":12.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919321","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}

{"title":"Elevated Cutaneous Interleukin‐21 Links Eczematous Eruption to Interleukin‐17A Inhibitor Treatment in Psoriasis","authors":"Li Zhang, Lihong Chen, Hailun Wang, Ce Shuai, Youcong Wang, Han Cao, Feng Xue, Jiayi Zhang, Meng Pan, Xia Li, Jie Zheng","doi":"10.1111/all.70026","DOIUrl":"https://doi.org/10.1111/all.70026","url":null,"abstract":"BackgroundEczematous eruption (EE) is an adverse effect observed in psoriasis patients undergoing interleukin (IL)‐17A inhibitor therapy, with reported incidence rates ranging from 2.2% to 12.1%. In some cases, this reaction leads to discontinuation of treatment. However, the underlying mechanism of EE development remains unclear. Therefore, we aimed to elucidate the pathogenesis of EE associated with anti‐IL‐17A treatment and identify pathogenic molecules involved.MethodsSkin samples were collected from psoriasis patients both before and after anti‐IL‐17A treatment, and the treated skin included those with and without EE. Transcriptomic profiling was performed using bulk RNA‐seq and scRNA‐seq, which were further validated by histopathological analysis and protein assay. In addition, in vitro experiments were conducted to explore the underlying mechanisms.ResultsBulk RNA‐seq analysis revealed significantly elevated IL‐21 expression in EE lesions, along with marked enrichment of Th2/Th22 pathways and activation of JAK–STAT signaling compared to baseline and non‐EE samples. Immunohistochemistry confirmed increased expression of IL‐21, pJAK1, and pSTAT3 in EE lesions. ELISA and LEGENDplex assays detected higher levels of IL‐21, IL‐13, and IL‐22, with positive correlations between IL‐21 and the latter two cytokines. ScRNA‐seq localized IL‐21 expression predominantly to T cells within EE lesions, which co‐expressed high levels of IL‐13 and IL‐22. In vitro, rhIL‐21 stimulation activated JAK1/STAT3 signaling and increased IL‐13 and IL‐22 secretion, which were suppressed by JAK1 inhibition. These findings identify IL‐21 as an important regulator of Th2/Th22 responses and JAK–STAT signaling in EE pathogenesis.ConclusionIL‐21 is an important inflammatory mediator contributing to the development of EE.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"8 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919131","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":"Myeloid cAMP Reduction Shifts Rhinovirus‐Induced Airway Inflammation From Neutrophilic to Eosinophilic by Suppressing M1‐Interstitial Macrophages","authors":"Seong Ok Park, Erdenebileg Uyangaa, Hyo Jin Kim, Hee Won Byeon, Jin Young Choi, Koanhoi Kim, Jihyung Lee, Samuel Bertin, Eyal Raz, Seong Kug Eo","doi":"10.1111/all.70018","DOIUrl":"https://doi.org/10.1111/all.70018","url":null,"abstract":"BackgroundAsthma exacerbations caused by human rhinovirus (hRV) infection are characterized by airway neutrophilia and reduced corticosteroid response, leading to significant healthcare costs and lung function impairment. The Gαs subunit of the trimeric G protein regulates immunopathological conditions by modulating cAMP levels. We aimed to investigate the impact of myeloid cAMP levels on neutrophil‐dominated asthma exacerbation caused by hRV infection.MethodsWe generated mice with myeloid cell‐specific deletion of the Gαs subunit by targeting the LysM gene, leading to a specific reduction of cAMP in myeloid cells. Neutrophilic asthma exacerbation was induced by hRV infection during allergen challenge, and cytokine production in BALF and lung tissue was assessed, along with histological examinations.ResultsMyeloid Gαs ablation was found to shift airway inflammation from a neutrophilic to an eosinophilic phenotype during hRV‐induced asthma exacerbation. This change led to mucus hypersecretion and Th2‐type inflammation, and enhanced CD4<jats:sup>+</jats:sup> Th2 effector cell expansion. In chronic asthma with repeated allergen and hRV exposure, myeloid Gαs ablation caused mixed Th2‐ and Th17‐biased inflammation with increased neutrophil and eosinophil infiltration and collagen deposition. Myeloid Gαs deficiency hindered NLRP3 inflammasome activation, thereby suppressing M1 polarization of interstitial macrophages during eosinophilic inflammation. cAMP levels in macrophages were likely associated with M1 polarization, as cAMP analogs regulated NLRP3 inflammasome activation via PKA and EPAC pathways. Finally, adoptive transfer of cAMP analog‐treated macrophages reversed eosinophilic to neutrophilic inflammation in myeloid Gαs‐ablated mice following hRV infection.ConclusionsThese results highlight the essential role of macrophage cAMP in steroid‐resistant, neutrophil‐dominant airway inflammation during hRV‐induced asthma exacerbation.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"47 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915606","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}