Journal of Allergy and Clinical Immunology最新文献

{"title":"Mesenchymal stem cell-derived small extracellular vesicles restored nasal barrier function in allergic rhinitis via miR-143-GSK3β in human nasal epithelial cells.","authors":"Meiqian Xu, Mei Ren, Xinyin Zhang, Wenxu Peng, Hao Li, Wenjing Liao, Jianlei Xie, Xiaowen Zhang","doi":"10.1016/j.jaci.2024.10.034","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.034","url":null,"abstract":"<p><strong>Background: </strong>The nasal epithelial barrier is the first line of defense against the deep entry of pathogens or aeroallergens, and is more critical in allergic rhinitis (AR). Restoring epithelial barrier dysfunction might be a promising strategy for AR. Recent studies reported that mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and promote tissue regeneration. However, their effect on nasal epithelial cells remains unknown.</p><p><strong>Objectives: </strong>This study sought to describe the therapeutic effect of MSC-sEV on AR, particularly focusing their effect on nasal epithelial cells and underlying molecular mechanisms.</p><p><strong>Methods: </strong>We utilized an ovalbumin (OVA)-induced mouse model to study AR. Both primary and immortalized human nasal epithelial cells were used to further validate the therapeutic effects of MSC-sEV on epithelial cell function. Then we constructed miR-143 overexpressing and low-expressing HNEpC and MSC-sEV to elucidate molecular mechanisms. Transcriptome analysis was performed to identify the downstream pathways involved.</p><p><strong>Results: </strong>MSC-sEV successfully maintained nasal barrier integrity in AR mouse model. The MSC-sEV therapeutic effect on the nasal barrier was substantiated in HNEpC. Mechanistically, microRNA (miR)-143 was a candidate mediator of the above effects. Subsequently, transfecting HNEpC with miR-143 partially mimicked the restoring effect of MSC-sEV. MSC-sEV overexpressing miR-143 exerted more therapeutic effects on tight junctions and barrier integrity. Moreover, miR-143 regulated the GSK3β pathway.</p><p><strong>Conclusions: </strong>Our results indicated that MSC-sEV mitigated AR and restored nasal epithelial barrier dysfunction through the miR-143-GSK3β axis, which suggested that MSC-sEV have the remarkable ability to treat AR.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620982","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":"Omalizumab for mast cell disorders.","authors":"Cem Akin","doi":"10.1016/j.jaci.2024.11.004","DOIUrl":"10.1016/j.jaci.2024.11.004","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620984","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":"Omalizumab Safety Concerns.","authors":"Thanai Pongdee, James T Li","doi":"10.1016/j.jaci.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.005","url":null,"abstract":"<p><p>IgE and mast cells play key roles in the pathophysiology of allergic diseases, and omalizumab was the first monoclonal anti-IgE antibody licensed in the U.S. when initially FDA-approved for the treatment of allergic asthma in 2003. Since that time, the number of FDA-approved indications for treatment with omalizumab has grown to include chronic spontaneous urticaria, chronic rhinosinusitis with nasal polyps, and food allergy. Although omalizumab is generally considered relatively safe and well-tolerated, a number of safety concerns have been raised since its initial approval. These concerns focus on specific adverse events of interest that include anaphylaxis, pregnancy, malignancy, cardiovascular events, and infections. For each of these issues, data from clinical trials and post-marketing surveillance has been extensively evaluated. In this review, we examine this safety data, provide context for safety and risk assessments, and summarize a safety profile for each of the adverse events of interest. In doing so, we aim to provide a resource for shared-decision making when treatment with omalizumab is being considered.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620986","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":"Low-dose interleukin-2 in birch pollen allergy: a phase-2 randomized double-blind placebo-controlled trial.","authors":"Michelle Rosenzwajg, Alina Gherasim, Franck Dietsch, Marine Beck, Nathalie Domis, Roberta Lorenzon, Yannick Chantran, Bertrand Bellier, E Vicaut, Angele Soria, Frederic De Blay, David Klatzmann","doi":"10.1016/j.jaci.2024.10.033","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.033","url":null,"abstract":"<p><strong>Background: </strong>Regulatory T cells (Tregs) are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2_LD) activates Tregs.</p><p><strong>Objective: </strong>To assess IL-2_LD efficacy for controlling clinical responses to allergen exposures.</p><p><strong>Methods: </strong>RHINIL-2 was a phase-2a, randomised, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included, 66% having concomitant asthma. All had a total nasal symptom score (TNSS) ≥5 following nasal exposure to BP in an environmental-exposure-chamber (EEC). Patients received 1 MUI/day of IL-2 (n=12) or Placebo (n=12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the EEC were evaluated using TNSS, the rhinitis visual analogue scale (VAS) and spirometry. The primary efficacy endpoint was the difference in TNSS area under the curve between inclusion and day 40 (TNSSΔAUC).</p><p><strong>Results: </strong>IL-2_LD treatment induced a significant expansion of Tregs. The TNSSΔAUC in the IL-2 and Placebo groups was non significantly different. TNSS and VAS AUCs were significantly reduced from baseline to day 40 in the IL-2_LD group only (p=0.04 and p=0.01, respectively). The ratio of forced expiratory volume in 1 second/forced vital capacity (FEV_1P) and the forced mid-expiratory flow (FEF_25-75%) showed improvement in the IL-2_LD vs Placebo groups at day 40 (p=0.04 and 0.04, respectively). However, the short treatment duration used in this study cannot have effects on specific IgE or IgG4 levels given their half-life. There was no severe treatment-related adverse events.</p><p><strong>Conclusion: </strong>IL-2_LD is well-tolerated in allergic patients, even with asthma, clearing the path for further therapeutic development. Our work suggests that Treg can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620980","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":"Update on Type 2 Immunity.","authors":"Magdalena M Gorska","doi":"10.1016/j.jaci.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.003","url":null,"abstract":"<p><p>This review article summarizes and comments on the mechanistic work on type 2 immunity published between January 2022 and September 2024. Type 2 immunity is characterized by the production of IL4, IL5, IL9 and IL13, and primarily known for its detrimental roles in allergic diseases and protective roles in helminth infections. Other functions of type 2 immunity include protection against venoms and toxins, wound healing, tissue remodeling, regeneration and metabolic homeostasis. This review article discusses novel findings on regulation of these processes and disease states by select cells and humoral factors of type 2 immunity, including group 2 innate lymphoid cells (ILC2s), CD4 T cells, mast cells, peripheral neurons and IgE. The article also describes novel discoveries on regulation of these factors and cells by environmental exposures and the host. Further, the article discusses select genetic mouse models that were developed recently and have the potential to accelerate the field. Finally, the article comments on the significance of novel discoveries to clinical medicine, including drug development.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621014","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":"Analysis of human neutrophils from nasal polyps by single-cell RNA sequencing reveals roles of neutrophils in chronic rhinosinusitis.","authors":"Naruhito Iwasaki, Julie A Poposki, Masanori Kidoguchi, Aiko Oka, Aiko I Klingler, Whitney W Stevens, Lydia A Suh, Junqin Bai, Anju T Peters, Leslie C Grammer, Kevin C Welch, Stephanie S Smith, David B Conley, Bruce S Bochner, Robert P Schleimer, Robert C Kern, Bruce K Tan, Atsushi Kato","doi":"10.1016/j.jaci.2024.10.032","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.032","url":null,"abstract":"<p><strong>Background: </strong>Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 (T2) inflammation. Recent studies, including our own, suggest that neutrophils are also elevated in T2 nasal polyps (NPs) and that elevated neutrophils display an activated phenotype. However, the actual roles of neutrophils in NP pathogenesis in T2 CRSwNP are still largely unclear.</p><p><strong>Objective: </strong>To reveal the roles and heterogeneity of neutrophils in NP tissue by single cell RNA-Sequencing (scRNA-Seq) analysis.</p><p><strong>Methods: </strong>We developed a novel microwell-based scRNA-Seq assay (BD Rhapsody platform) using granulocyte enriched samples from 5 control sinus tissues (CTs), 5 NP tissues and patient matched peripheral blood (PB) samples. This approach allowed for the examination of differential expression of genes in NP neutrophils by the Benjamini-Hochberg algorithm and predicted the overall function of NP neutrophils by pathway and gene ontology (GO) enrichment analyses.</p><p><strong>Results: </strong>After all QC steps, we successfully detected neutrophils. We identified 333 down-regulated and 128 up-regulated genes in NP neutrophils (1,151 cells) compared to all PB neutrophils (13,591 cells) (>1.5-fold, q<0.05), and found commonly dysregulated genes in NP neutrophils compared to both all PB and CT neutrophils (3,136 cells). Commonly down-regulated genes in NP neutrophils were associated with the innate immune system, and up-regulated genes were associated with NF-κB signaling, cytokine activity and cellular response to oxygen-containing compounds. NP neutrophils displayed 4 clusters revealing potential heterogeneity of neutrophils in NP tissue.</p><p><strong>Conclusions: </strong>Elevated neutrophils in NP tissue appear to exist in several subphenotypes that may play important pathogenic roles in CRSwNP.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620952","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":"Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis.","authors":"Stephan Weidinger, Andrew Blauvelt, Kim A Papp, Adam Reich, Chih-Hung Lee, Margitta Worm, Charles Lynde, Yoko Kataoka, Peter Foley, Xiaodan Wei, Wanling Wong, Anne-Catherine Solente, Christine Weber, Samuel Adelman, Sonya Davey, Fabrice Hurbin, Natalie Rynkiewicz, Karl Yen, John T O'Malley, Charlotte Bernigaud","doi":"10.1016/j.jaci.2024.10.031","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.031","url":null,"abstract":"<p><strong>Background: </strong>Amlitelimab, a fully human nondepleting monoclonal antibody targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD).</p><p><strong>Objective: </strong>This trial evaluated the efficacy and safety of amlitelimab in adults with AD.</p><p><strong>Methods: </strong>In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg with 500-mg loading dose, 250 mg, 125 mg, or 62.5 mg, or placebo for 24 weeks in Part 1 (1:1:1:1:1 randomization). In Part 2, clinical responders were reallocated 3:1 to withdraw amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percent change in Eczema Area and Severity Index (EASI) from baseline to Week 16.</p><p><strong>Results: </strong>390 and 190 patients enrolled in Part 1 and Part 2, respectively. Significant percent change decreases in EASI were observed with amlitelimab vs. placebo (P<.001). Clinical responses at Week 24 (Investigator Global Assessment 0/1 and/or EASI-75) were maintained at Week 52 in patients continuing or withdrawn from amlitelimab. In patients maintaining clinical response at Week 52 while off-treatment, >80% had serum amlitelimab concentrations below a 4-μg/mL threshold for several weeks prior to Week 52. Reductions in AD-related biomarkers during Part 1 were maintained through Part 2. Amlitelimab was well tolerated over 52 weeks.</p><p><strong>Conclusions: </strong>Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through Week 52. Sustained responses were observed in the majority of patients after amlitelimab withdrawal for 28 weeks.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620988","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":"Profiling immune cell tissue niches in the spatial \"omics\" era.","authors":"Colin Yc Lee, James McCaffrey, Dominic McGovern, Menna R Clatworthy","doi":"10.1016/j.jaci.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.001","url":null,"abstract":"<p><p>Immune responses require complex, spatially-coordinated interactions between immune cells and their tissue environment. For decades, we have imaged tissue sections to visualise a limited number of immune-related macromolecules in situ, functioning as surrogates for cell types or processes of interest. However, this inevitably provides a limited snapshot of the tissue's immune landscape. Recent developments in high-throughput spatial \"omic\" technologies, particularly spatial transcriptomics, and its application to human samples has facilitated a more comprehensive understanding of tissue immunity, by mapping fine-grained immune cell states to their precise tissue location, while providing contextual information about their immediate cellular and tissue environment. These data provide opportunities to investigate mechanisms underlying the spatial distribution of immune cells and its functional implications, including the identification of \"immune niches\", although the criteria used to define this term have been inconsistent. Here, we review recent technological and analytical advances in multi-parameter spatial profiling, focussing on how these methods have generated new insights in translational immunology. We propose a 3-step framework for the definition and characterisation of immune niches, which is powerfully facilitated by new spatial profiling methodologies. Finally, we summarise current approaches to analyse adaptive immune repertoires and lymphocyte clonal expansion in a spatially-resolved manner.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620992","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":"Reply.","authors":"Pedro A Lamothe, Martin C Runnstrom, F Eun-Hyung Lee","doi":"10.1016/j.jaci.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.003","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620998","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":"Impact of biologics on the immune response to mRNA COVID-19 vaccination in patients with asthma.","authors":"Shu-Yi Liao, Barry Make, Michael E Wechsler","doi":"10.1016/j.jaci.2024.09.028","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.028","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620974","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}