Allergy, Asthma & Immunology Research最新文献

{"title":"Cold Urticaria: From Wheals to Anaphylaxis.","authors":"Mojca Bizjak","doi":"10.4168/aair.2025.17.5.547","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.547","url":null,"abstract":"<p><p>Cold urticaria (ColdU) is characterized by wheals, angioedema, or both, which are triggered by exposure to cold. A subset of patients experiences cold-induced anaphylaxis (ColdA), a potentially life-threatening systemic reaction. The pathogenesis of ColdU remains incompletely understood, but mast cell activation plays a central role. Most hypotheses are decades old and require further investigations. ColdU and ColdA are clinically diagnosed and typically supported by cold stimulation testing (CST). However, standard CST methods may yield negative results despite a clear clinical history. ColdU is classified into typical and atypical forms based on CST responses. ColdA occurs more frequently in patients with mucosal angioedema involving the oropharynx. It is most commonly triggered by full-body cold exposure, such as swimming. Diagnostic workup should include a detailed history, CST, and evaluation for underlying conditions, particularly in patients with clinical signs and symptoms extending beyond the skin. First-line treatment involves second-generation H₁-antihistamines, often needed at increased doses for disease control. Omalizumab has shown efficacy in clinical trials and case reports for refractory cases. Adrenaline is the first-line therapy for ColdA; high-risk patients should be prescribed autoinjectors and receive proper training in their use. This review provides an overview of the pathophysiology, classification, diagnostic procedures, and management of ColdU and ColdA, emphasizing clinical variability and unmet research needs.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"547-562"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in Peanut Allergy: The Present and the Future.","authors":"Kangmo Ahn","doi":"10.4168/aair.2025.17.5.527","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.527","url":null,"abstract":"","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"527-530"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Reveals a Distinct Monocyte MIF/ANXA1 Signature Associated With Poor Responsiveness to ICS.","authors":"Haeyoon Kwon, Minji Kang, Soyoung Jeong, Moonki Chae, Hyun Seung Lee, Brian Hyohyoung Lee, Hyo Jeong Nam, Heung-Woo Park, Suh-Young Lee, Hyun Je Kim","doi":"10.4168/aair.2025.17.5.658","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.658","url":null,"abstract":"<p><p>Inhaled corticosteroids (ICSs) are the foundation of asthma management, yet a subset of patients exhibits poor clinical response despite adequate treatment. Understanding the cellular and molecular mechanisms underlying this heterogeneity is essential for developing targeted therapies. We performed single-cell RNA sequencing on peripheral blood mononuclear cells from 6 healthy controls, 6 ICS responders, and 4 ICS poor responders with asthma. We analyzed transcriptional profiles of immune cell subsets, focusing on CD14+ monocytes, and assessed signaling pathways using differential gene expression and receptor-ligand interaction analysis. ICS poor responders exhibited a reduced frequency of circulating CD14+ monocytes and upregulation of chemotaxis-related genes, including <i>CCR1</i>, <i>CCL2</i>, <i>CCL7</i>, and <i>CXCL2</i>. <i>ANXA1</i> and its receptor <i>FPR2</i>, key regulators of anti-inflammatory responses, were downregulated in poor responders, while <i>MIF</i> and its receptors were upregulated. Receptor-ligand analysis identified T cells as a potential paracrine source of MIF signaling. Our findings highlight MIF-ANXA1 dysregulation in CD14+ monocytes as a key immune signature associated with poor ICS response in asthma.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"658-667"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clustering CRSwNP Patients for Predicting Uncontrolled Outcomes Based on Clinical Features.","authors":"Ying Chen, Jianwei Wang, Yu Zhang, Yisong Yao, Xinjun Xu, Pengyi Yu, Jing Guo, Yujuan Yang, Jiali Yin, Zhen Liu, Huifang Liu, Ting Zuo, Bei Zhang, Xicheng Song","doi":"10.4168/aair.2025.17.5.628","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.628","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic rhinosinusitis with nasal polyps (CRSwNP) is highly complex and heterogeneous. Many patients still respond poorly to current medications that combine with surgical treatment strategies, resulting in uncontrolled outcomes. However, identifying uncontrolled CRSwNP remains challenging. We aimed to develop an effective predictive procedure to assess uncontrolled CRSwNP based on clinical features.</p><p><strong>Methods: </strong>The clinical features of 952 adult CRSwNP patients were subjected to a decision tree analysis, with the uncontrolled outcome at follow-up considered the positive predictive event.</p><p><strong>Results: </strong>A predictive procedure was developed to categorized CRSwNP patients into 6 clusters with different uncontrolled rates. classification indicators were determined as the total computed tomography (CT) scores and age, as well as tissue and blood eosinophil counts . The uncontrolled rates in Clusters 1-6 were 2.75%, 12.31%, 21.28%, 33.16%, 13.54%, and 38.27%, respectively. Additionally, Cluster 1 patients had the lowest tissue and blood eosinophil count and ratio, and the lowest total CT score. Cluster 3 patients had the highest tissue eosinophil count and ratio. Cluster 5 patients >2-fold tissue eosinophil count and ratio than Cluster 2 patients. Cluster 6 patients had the highest value for blood eosinophil count and ratio, total CT score, and endoscopic score. After surgery, the primary disturbing symptoms were nasal congestion (11.01% in Cluster 1 patients and 22.31% in Cluster 2 patients), rhinorrhea/postnasal drip (27.66% in Cluster 3 patients), and olfactory dysfunction (43.68%, 26.56%, and 50.62% in Clusters 4-6 patients, respectively).</p><p><strong>Conclusions: </strong>The decision tree constructed from the total CT scores, tissue and blood eosinophil counts, and age can generate an effective predictive procedure to guide the identification of uncontrolled CRSwNP.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"628-639"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing Systemic Reactions During Subcutaneous Immunotherapy for House Dust Mite Allergies in China: Insights From a Cluster Analysis Study.","authors":"Qingxiu Xu, Jinling Liu, Xiang Dong, Lisha Li, Hao Chen, Yin Wang, Hongting Zhang, Juan Meng, Kai Guan, Pascal Demoly, Rongfei Zhu","doi":"10.4168/aair.2025.17.5.578","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.578","url":null,"abstract":"<p><strong>Purpose: </strong>Subcutaneous immunotherapy (SCIT) can trigger systemic reactions (SRs) that pose potential life-threatening risks. To date, no cluster analysis has been conducted to delineate sub-phenotypes of SRs. This study aims to identify and characterize diverse SR phenotypes during SCIT for house dust mite (HDM) allergies in China.</p><p><strong>Methods: </strong>This large retrospective real-world study enrolled patients diagnosed with HDM-sensitized allergic rhinitis (AR) and/or asthma who underwent SCIT (Alutard SQ; ALK) between February 2013 and July 2024 at five allergy centers in China. Data on demographic profiles and SRs were collected, followed by a cluster analysis among SR patients.</p><p><strong>Results: </strong>A total of 3,126 patients received 107,588 injections, with SRs observed in 354 patients (11.32%) and 1,056 injections (0.98%). A higher incidence of SRs was noted in younger patients (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.88-0.92; <i>P</i> < 0.001), those with asthma (OR, 2.12; 95% CI, 1.69-2.66; <i>P</i> < 0.001), those with longer disease duration (OR, 1.08; 95% CI, 1.04-1.12; <i>P</i> < 0.001), those with high sensitization (OR, 3.84; 95% CI, 1.66-8.88; <i>P</i> = 0.002), and those with polysensitization (OR, 1.69; 95% CI, 1.30-2.20; <i>P</i> < 0.001). Four distinct clusters of SRs were identified: Cluster 1 (16.5%) primarily comprised relatively older females with lower specific immunoglobulin E (sIgE) levels, predominantly cutaneous involvement, fewer SRs overall but with grade 4 SR; Cluster 2 (29.9%) mainly included AR patients without asthma, mostly exhibiting grade 1 SR; Cluster 3 (34.0%) predominantly consisted of asthma patients with monosensitization, higher injection doses, and mostly grade 2 SR; Cluster 4 (19.6%) mainly featured younger males with higher sIgE levels, polysensitization, lower injection doses, the highest number of SRs, and more grade 3 SR.</p><p><strong>Conclusions: </strong>Asthma, disease duration, high sensitization, and polysensitization emerge as independent risk factors for SRs. Our cluster analysis delineates distinct clinical phenotypes of SRs, offering tailored interventions for the personalized management of patients experiencing SRs.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"578-591"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transdermal Allergen-Specific Immunotherapy Using a Biodegradable Microneedle Array Patch in a Murine Model of Peanut Anaphylaxis.","authors":"Hye Jeong Yun, Eun Yi Oh, Hyeonho Kim, Dong Jun Kim, Sung Hyun Kim, Yeji Shin, Jitae Kim, Kwang Hoon Lee, JooYeon Jhun, Mi-La Cho, Do Hyeon Jeong, Kyoung Yong Jeong, Jung-Won Park","doi":"10.4168/aair.2025.17.5.640","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.640","url":null,"abstract":"<p><strong>Purpose: </strong>Peanut anaphylaxis is a widespread challenge, particularly in children. We aimed to confirm the therapeutic effects of transdermal immunotherapy (TDIT) in a murine model of peanut anaphylaxis.</p><p><strong>Methods: </strong>We developed a biodegradable microneedle array patch (MAP) by incorporating peanut extract (PE) with hyaluronic acid. The allergenicity of the PE in MAP was assayed by enzyme-linked immunosorbent assay inhibition. The peanut anaphylaxis model was made with BALB/c or C3H/Hej mouse strains. We measured anaphylaxis clinical scores, as well as the levels of mouse mast cell protease-1 (MCPT-1), PE-specific immunoglobulin E (sIgE), specific immunoglobulin G (sIgG)1, and sIgG2a in serum. T cell populations in the spleen and jejunum were examined using immunohistochemical stains with confocal microscopy. Histological analysis of the jejunum was performed. The production of T helper cell type 2 (Th2) and regulatory T cell (Treg) cytokines by stimulated splenocytes were also measured.</p><p><strong>Results: </strong>The inhibitory capacity of the PE in MAP for PE sIgE was comparable to that of native PE. TDIT with 10 μg of PE-MAP recovered anaphylaxis score, sIgE, and the MCPT-1 levels, and enhanced sIgG1 and sIgG4 in serum. TDIT also reduced the recruitment of Th2 cells while increasing Treg and Th1 cells in both the spleen and jejunum. However, the efficacy of applying 10 μg of PE-MAP TDIT twice a week was more pronounced than applying once a week. Additionally, TDIT led to reduced production of Th2 cytokines (interleukin [IL]-4, IL-5, IL-13) and increased production of transforming growth factor-β by stimulated splenocytes. TDIT attenuated inflammation, mast cell infiltration, and villous damage in the jejunum.</p><p><strong>Conclusions: </strong>PE-MAP TDIT demonstrated therapeutic effects in peanut anaphylaxis, suggesting its potential for developing a novel TDIT for patients with peanut anaphylaxis.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"640-657"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview of Chronic Spontaneous Urticaria: Diagnosis, Management, and Treatment.","authors":"Bushra Tbakhi, Kaleb Ware, Hae-Sim Park, Joshua S Bernstein, Jonathan A Bernstein","doi":"10.4168/aair.2025.17.5.531","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.531","url":null,"abstract":"<p><p>Chronic spontaneous urticaria (CSU) is a complex mast cell-driven disorder characterized by recurrent pruritic wheals and/or angioedema lasting over 6 weeks. This condition affects women more frequently than men, particularly between the ages of 20 and 40, and imposes considerable physical, psychological, and economic burdens, with annual healthcare costs in the U.S exceeding $200 million. Current management strategies emphasize a stepwise approach, initiating with the escalating doses of second-generation antihistamines, followed by biologics such as omalizumab or now dupilumab, and prescribing cyclosporine to refractory cases. Emerging therapies targeting specific endotypes of CSU, including Bruton's tyrosine kinase inhibitors and mast cell depleting agents, present new avenues for personalized treatment. Furthermore, validated patient-reported outcome measures and digital tools like the CRUSE application enhance symptom tracking and facilitate patient-physician communication. As the therapeutic landscape for CSU evolves, a focus on individualized, evidence-based care approaches is critical to optimizing patient outcomes. Future research priorities include identifying biomarkers predictive of treatment response, conducting long-term outcome studies, and evaluating treatment tapering strategies to achieve sustained remission. Addressing cost-effectiveness and accessibility of new therapies will be pivotal in ensuring equitable management of CSU across diverse populations. Ultimately, it is the goal that a comprehensive understanding of CSU's heterogeneity, with tailored therapeutic strategies, will significantly improve patient quality of life and outcomes.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"531-546"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Clinical and Cytokine Features of Moderate-Severe Persistent AR Phenotype by ARIA Classification: COCOA.","authors":"Da Kyeong Lee, Jisun Yoon, Hyo-Won Lee, Seung-Hwa Lee, Eun Young Baek, Eom Ji Choi, Kun Baek Song, Min Jee Park, Kangmo Ahn, Jihyun Kim, Kyung Won Kim, Youn Ho Shin, Dong In Suh, Ji Soo Park, So-Yeon Lee, Soo-Jong Hong","doi":"10.4168/aair.2025.17.5.563","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.563","url":null,"abstract":"<p><strong>Purpose: </strong>The prevalence of allergic rhinitis (AR) has increased rapidly. However, the AR phenotype in the general population remains poorly explored. In this study, we aimed to determine the distinct features of AR phenotypes according to Allergic Rhinitis and its Impact on Asthma (ARIA) classification in Korean children.</p><p><strong>Methods: </strong>We enrolled 1,113 children aged 7 years from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study. AR was diagnosed by a physician at each scheduled visit, and the AR phenotype was defined according to the ARIA classification. We analyzed the results of skin prick tests and performed cytokine assays using blood samples collected at ages 3 and 7.</p><p><strong>Results: </strong>The prevalence of AR at age 7 was 48.9%, while that of moderate-to-severe persistent AR phenotype was 4.4%. Cesarean delivery was associated with the mild-intermittent AR phenotype, while prenatal antibiotic use was linked to the moderate-to-severe persistent phenotype. Sensitization to <i>Dermatophagoides pteronyssinus</i> (<i>Der p</i>), <i>Dermatophagoides farinae</i> (<i>Der f</i>), birch, and Japanese hop at age 3 and sensitization to <i>Der p</i>, <i>Der f</i>, birch, oak, and cat at age 7 increased the risk of moderate-to-severe persistent AR phenotype. Upon cytokine analysis, interleukin (IL)-4 tended to be elevated at age 3 in children with moderate-to-severe persistent AR. By age 7, concentrations of IL-5 and IL-17A were significantly higher in children with moderate-to-severe persistent AR phenotype.</p><p><strong>Conclusions: </strong>These findings suggest that 4.4% of Korean children had a moderate-to-severe persistent AR phenotype, as defined by ARIA. Early sensitization to <i>Der p</i>, <i>Der f</i>, birch, and Japanese hop at age 3 and prenatal antibiotic use are risk factors. Furthermore, this phenotype may involve both T helper 2 and T helper 17-related immune responses, reflecting a potential shift toward more complex or mixed patterns of inflammation.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"563-577"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Metabolomic Biomarkers of Middle-Adulthood to Late-Adulthood Atopic Dermatitis: A Prospective Cohort Study From the UK Biobank.","authors":"Ha-Na Kim, John C Newman, Ji Hyun Lee","doi":"10.4168/aair.2025.17.5.615","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.615","url":null,"abstract":"<p><strong>Purpose: </strong>Although atopic dermatitis (AD) in adults has been prevalent, there has been a paucity of previous studies on the metabolic markers linked to its development. We investigated whether plasma metabolomic biomarkers are associated with incident middle-adulthood to late-adulthood AD and identified its predictors.</p><p><strong>Methods: </strong>This study utilized data collected from the UK Biobank between 2006 and 2010. We prospectively analyzed metabolites in 79,414 participants aged 40 to 69 years, predominantly of European ancestry and free of AD, to assess the incidence of AD, which were collected using the International Classification of Diseases from hospital inpatient admission records from the baseline through 2022. The relationship between these metabolites and the incidence of AD was estimated using Cox proportional hazard models, and the predictive value of the metabolites for the incidence of middle-adulthood to late-adulthood AD was assessed.</p><p><strong>Results: </strong>The incidence rate of middle-adulthood to late-adulthood AD was 7.81 per 10,000 person-years, and the median follow-up was 161 months. A total of 35 plasma metabolites included in lipoprotein lipids, fatty acids, amino acids, and biomarkers related to fluid balance were significantly linked to the risk of middle-adulthood to late-adulthood AD incidence. Significant non-linear associations of middle-adulthood to late-adulthood AD incidence were observed with triglycerides in medium very-low density lipoprotein, leucine, and the total concentration of branched-chain amino acids. The incorporation of the identified 35 metabolites with the covariates for middle-adulthood to late-adulthood AD risk prediction achieved an area under the curve of 0.71 (95% confidence interval, 0.67-0.75) and reclassification ability (net reclassification improvement = 21.4%, <i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>Findings from this prospective study suggest that the identified plasma metabolites could better clarify the underlying metabolic vulnerabilities and improve risk prediction associated with the development of middle-adulthood to late-adulthood AD.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"615-627"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-17D Attenuates OVA-induced Airway Inflammation and Remodeling Partially via the CD93 Receptor.","authors":"Shuochuan Shi, Jintao Zhang, Yun Pan, Xiaofei Liu, Rong Zeng, Changjuan Xu, Ying Wang, Qian Qi, Zhi Guo, Chengfang Yao, Ju Liu, Jianwen Fei, Li Li, Liang Dong","doi":"10.4168/aair.2025.17.5.592","DOIUrl":"https://doi.org/10.4168/aair.2025.17.5.592","url":null,"abstract":"<p><strong>Purpose: </strong>Airway inflammation and remodeling are pivotal in asthma pathogenesis. Interleukin-17D (IL-17D), a recently characterized cytokine within the IL-17 family, is found to be expressed at higher levels in lung tissue; however, its role in asthma remains unclear. This study aims to elucidate the function and mechanisms of IL-17D in asthma, providing new insights for therapeutic strategies.</p><p><strong>Methods: </strong>We analyzed IL-17D messenger RNA expression levels using datasets from the Gene Expression Omnibus (GEO). Bronchoscopic biopsy tissues and serum samples from asthmatics, along with lung tissues from chronic asthmatic mice, were collected to validate IL-17D expression. Lentivirus-mediated IL-17D knockdown was performed in a chronic asthma mouse model induced by ovalbumin (OVA). Recombinant murine IL-17D protein was intranasally administered to further investigate its impact. <i>In vitro</i>, human bronchial epithelial cells (16HBE) were treated with recombinant human IL-17D or CD93-targeting small interfering RNA to explore signaling mechanisms.</p><p><strong>Results: </strong>GEO data and experimental findings revealed that IL-17D expression was reduced in the airway epithelia of asthmatics and chronic asthmatic mice. <i>In vivo</i>, knockdown of IL-17D exacerbated peri-airway inflammation and promoted epithelial-mesenchymal transition (EMT) in OVA-induced asthmatic mice. Conversely, recombinant IL-17D protein administration significantly attenuated airway inflammation, extracellular matrix (ECM) deposition, and EMT progression. In vitro, IL-17D mitigated transforming growth factor-β1-induced fibrotic remodeling in 16HBE cells, with CD93 receptor silencing partially reversing these effects.</p><p><strong>Conclusions: </strong>Our findings suggest that IL-17D could play a protective role in asthmatic airway inflammation and remodeling, partially through the CD93 receptors. These results highlight IL-17D as a potential therapeutic target for asthma management.</p>","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"17 5","pages":"592-614"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}