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The nasal microbiome in early infancy is primarily shaped by the maternal nasal microbiome. 婴儿早期的鼻腔微生物群主要由母体的鼻腔微生物群形成。
IF 14.2 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-16 DOI: 10.1016/j.jaci.2025.05.004
Bailey E Quinn,José Alejandro Reyes Rodríguez,Emmanuel Kweku Sam,Jasmina Duliman,Elizabeth Denn,Sandra Lee,Liang Shan,Christiana Kuti,Beatrice Irene Nyann,Nicolas Rosario-Matos,Leyao Wang
{"title":"The nasal microbiome in early infancy is primarily shaped by the maternal nasal microbiome.","authors":"Bailey E Quinn,José Alejandro Reyes Rodríguez,Emmanuel Kweku Sam,Jasmina Duliman,Elizabeth Denn,Sandra Lee,Liang Shan,Christiana Kuti,Beatrice Irene Nyann,Nicolas Rosario-Matos,Leyao Wang","doi":"10.1016/j.jaci.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.05.004","url":null,"abstract":"BACKGROUNDThe infant nasal microbiota closely mediates the risks of developing childhood respiratory diseases. However, the primary sources of these early residing bacteria remain largely unknown, preventing the development of microbiome strategies for disease prevention.OBJECTIVEIdentify the primary maternal source of bacteria found in the early infant nasal microbiome.METHODSWe conducted a birth cohort study, named Mother Infant Microbiome International Cohort (MIMIC). We recruited 95 mother-newborn dyads from three sites (St. Louis, Missouri, United States; San Juan, Puerto Rico; and Accra, Ghana) and collected samples at two time points (at birth and around two months of age). We performed analyses on 16S ribosomal RNA gene sequencing data to evaluate the maternal microbiomes (nasal, saliva, breast milk, and areola skin) as sources seeding the infant nasal microbiome.RESULTSThe infant nasal microbiome underwent a major compositional change during the first two months of life. The maternal nasal microbiome was identified as the primary source of bacteria in the early nasal microbiome across the three regions. Corynebacterium was predominantly transferred from the maternal nasal microbiome. Infants were more likely to harbor a Corynebacterium-dominant nasal microbiome if their mother's nasal microbiome was Corynebacterium-dominant.CONCLUSIONSThe maternal nasal microbiome is an important source of bacteria in the early nasal microbiome. A large portion of transmitted bacteria from the maternal nasal microbiome was a generally beneficial bacterial genus, Corynebacterium. Results from this study will aid the development of early life intervention strategies that aim to reduce the incidence of childhood respiratory diseases and asthma.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"77 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087529","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}
引用次数: 0
Cannabinoid WIN55,212-2 restores bronchial epithelium by regulating oxidative stress and STAT6 phosphorylation. 大麻素WIN55,212-2通过调节氧化应激和STAT6磷酸化来恢复支气管上皮。
IF 14.2 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-16 DOI: 10.1016/j.jaci.2025.05.002
Mario Pérez-Diego,Alba Angelina,Yağız Pat,Angel Maldonado,Carmen Sevilla-Ortega,Leticia Martín-Cruz,Duygu Yazici,Beate Rückert,Milena Sokolowska,Mar Martín-Fontecha,Mübeccel Akdis,Cezmi A Akdis,Oscar Palomares
{"title":"Cannabinoid WIN55,212-2 restores bronchial epithelium by regulating oxidative stress and STAT6 phosphorylation.","authors":"Mario Pérez-Diego,Alba Angelina,Yağız Pat,Angel Maldonado,Carmen Sevilla-Ortega,Leticia Martín-Cruz,Duygu Yazici,Beate Rückert,Milena Sokolowska,Mar Martín-Fontecha,Mübeccel Akdis,Cezmi A Akdis,Oscar Palomares","doi":"10.1016/j.jaci.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.05.002","url":null,"abstract":"BACKGROUNDViral infections and type 2 immune responses perpetuate airway epithelial barrier dysfunction and inflammation, leading to the development and progression of asthma. The synthetic cannabinoid WIN55,212-2 displays anti-inflammatory properties by acting on different immune system cells.OBJECTIVESTo investigate the capacity of WIN55,212-2 to restore bronchial epithelial barrier function in asthma in the context of viral infections or type 2-driven inflammation.METHODSAir-liquid-interface (ALI) cultures of human bronchial epithelial cells and human bronchial epithelial spheroids were generated to assess the capacity of WIN55,212-2 to restore airway epithelial barrier damage induced by human rhinovirus A16 (RV-A16) infection or type 2 inflammation. RT-PCR, cytokine quantification, permeability assays, metabolic studies, flow cytometry and western blot techniques were employed to assess the effects of WIN55,212-2 on the airway epithelium. The in vivo relevance of our findings was evaluated in a murine model of IL-13-induced airway inflammation.RESULTSProphylactic and therapeutic administration of WIN55,212-2 accelerated the recovery from RV-A16-induced bronchial epithelial barrier damage. WIN55,212-2 inhibited the acquisition of IL-13-induced type 2 asthma features in ALI cultures, self-assembled bronchial epithelial spheroids and in vivo asthma model of airway inflammation and epithelial dysfunction. Mechanistically, WIN55,212-2 impaired IL-13-induced oxidative stress in epithelial cells restoring the activity of protein tyrosine phosphatases, which in turn inhibits pSTAT6-mediated signaling pathways and asthma features.CONCLUSIONSThe cannabinoid WIN55,212-2 displays airway epithelial barrier protective effects during RV-A16 infection or type 2 inflammation by mechanisms associated to the modulation of oxidative metabolism and pSTAT6-mediated signaling.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"50 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087530","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}
引用次数: 0
Regulation of immune cell metabolism by therapeutic normal IgG intravenous immunoglobulin. 治疗性正常IgG静脉注射免疫球蛋白对免疫细胞代谢的调节。
IF 14.2 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-16 DOI: 10.1016/j.jaci.2025.05.003
Naresh Rambabu,Fawaz Alzaid,Boban D Anđelković,Sruthi Vijaya Retnakumar,Anupama Karnam,Srinivasa Reddy Bonam,Lucie Orliaguet,Tina Ejlalmanesh,Dorothy Tonui,Emeline Chu-Van,Ludovic Brunet,Nina Bozinovic,Ivan Nemazanyy,Fabian Käsermann,Nicolas Venteclef,Srini V Kaveri,Thibaut Léger,François Fenaille,Benoit Colsch,Jagadeesh Bayry
{"title":"Regulation of immune cell metabolism by therapeutic normal IgG intravenous immunoglobulin.","authors":"Naresh Rambabu,Fawaz Alzaid,Boban D Anđelković,Sruthi Vijaya Retnakumar,Anupama Karnam,Srinivasa Reddy Bonam,Lucie Orliaguet,Tina Ejlalmanesh,Dorothy Tonui,Emeline Chu-Van,Ludovic Brunet,Nina Bozinovic,Ivan Nemazanyy,Fabian Käsermann,Nicolas Venteclef,Srini V Kaveri,Thibaut Léger,François Fenaille,Benoit Colsch,Jagadeesh Bayry","doi":"10.1016/j.jaci.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.05.003","url":null,"abstract":"BACKGROUNDImmune cell metabolism and metabolic end-products influence the nature and magnitude of immune responses. Various autoimmune and inflammatory diseases are associated with dysregulated cellular metabolism. Intravenous immunoglobulin (IVIG), a therapeutic pooled normal IgG, is extensively used for the immunotherapy of a wide-range of autoimmune and inflammatory diseases. Although several cellular and molecular mechanisms of action of IVIG have been reported, the role of IVIG in modulating the immune cell metabolism remains unknown.OBJECTIVESTo investigate the influence of IVIG on the metabolic events of human immune cells.METHODSWe performed metabolic flux analyses on inflammatory mediators-stimulated human peripheral blood mononuclear cells (PBMCs). Further, intracellular metabolites were extracted from activated PBMCs and subjected to liquid chromatography coupled to high-resolution mass spectrometry. Untargeted global metabolic profiling of PBMCs was performed to determine the metabolic landscape of immune cells and metabolic reprogramming by IVIG. Targeted lipidomics was used for the mechanistic studies on IVIG-induced lipogenesis.RESULTSIVIG, and its Fc and F(ab')2 fragments regulate the Warburg effect in activated PBMCs depending on the glucose availability. Untargeted global metabolic profiling revealed that IVIG alters the overall metabolic landscape of inflammatory mediators-stimulated PBMCs, blocks prenylation of amino acid cysteine and promotes lipogenesis of well-known anti-inflammatory lipids like diacylglycerol and triacylglycerol by shuttling acetyl-CoA away from the mevalonate pathway. Mechanistically, IVIG-induced lipogenesis was mediated via F(ab')2 fragments and dependent on the sialylated glycans of IgG.CONCLUSIONSOur data indicate that IVIG targets immune cell metabolism and highlights a novel mechanism of action of IVIG in the context of immunotherapy of autoimmune and inflammatory diseases.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"97 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087527","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}
引用次数: 0
Tryptophan-kynurenine metabolites associate with inflammation and immunologic phenotypes in common variable immunodeficiency. 色氨酸-犬尿氨酸代谢物与常见可变免疫缺陷的炎症和免疫表型相关。
IF 14.2 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-14 DOI: 10.1016/j.jaci.2025.04.031
Silje F Jørgensen,Peder R Braadland,Thor Ueland,Mai S A Fraz,Annika E Michelsen,Kristian Holm,Liv T Osnes,Marius Trøseid,Per Magne Ueland,Børre Fevang,Pål Aukrust,Johannes R Hov
{"title":"Tryptophan-kynurenine metabolites associate with inflammation and immunologic phenotypes in common variable immunodeficiency.","authors":"Silje F Jørgensen,Peder R Braadland,Thor Ueland,Mai S A Fraz,Annika E Michelsen,Kristian Holm,Liv T Osnes,Marius Trøseid,Per Magne Ueland,Børre Fevang,Pål Aukrust,Johannes R Hov","doi":"10.1016/j.jaci.2025.04.031","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.031","url":null,"abstract":"BACKGROUNDA large proportion of patients with common variable immunodeficiency (CVID) have autoimmune and inflammatory manifestations characterized by chronic T-cell- and monocyte/macrophage activation of unknown etiology. The tryptophan-kynurenine pathway has previously been linked to immune activation involving T cells and monocytes/macrophages, as well as with gut microbial dysbiosis in some inflammatory diseases.OBJECTIVEWe aimed to characterize the tryptophan-kynurenine pathway in CVID and its potential association with clinical/immunologic phenotype and gut microbial dysbiosis.METHODSSerum concentrations of a set of tryptophan-kynurenine pathway metabolites and neopterin were measured using liquid chromatography-tandem mass spectrometry in a discovery cohort (n = 40), a validation cohort (n = 53), and healthy controls (n = 60). B-cell phenotype was analyzed in both cohorts, whereas inflammatory markers (enzyme immunoassay), lipopolysaccharide, gut microbial composition, and food frequency questionnaire were measured in the discovery cohort.RESULTSCompared to healthy controls, CVID patients had increased metabolism of the tryptophan-kynurenine pathway as assessed by increased kynurenine/tryptophan ratio, quinolinic acid, and 3-hydroxykynurenine in both the discovery and validation cohorts. The findings were most pronounced in the subgroup with autoimmune/inflammatory complications but was to some degree also observed in CVID patients with infection only. In CVID, the metabolites in the tryptophan-kynurenine pathway associated with soluble (s) markers of monocyte (sCD14, sCD163, neopterin) and T-cell (sCD25) activation as well as B-cell phenotype (eg, naïve B cells). Individual gut microbial taxa may influence tryptophan-kynurenine pathway metabolites, but not lipopolysaccharide or diet.CONCLUSIONWe found altered levels of several metabolites in the tryptophan-kynurenine pathway in two different CVID cohorts associated with systemic inflammation and B-cell phenotype.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"75 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083364","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}
引用次数: 0
The impact of allogeneic hematopoietic stem cell transplantation on pulmonary complications in adults with inborn errors of immunity. 异基因造血干细胞移植对先天性免疫缺陷成人肺部并发症的影响。
IF 14.2 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-14 DOI: 10.1016/j.jaci.2025.04.032
Aurélie Le Gal,Ambroise Marcais,Céline Goyard,Anne-Laure Brun,Morgane Cheminant,Nizar Mahlaoui,Claire Givel,Colas Tcherakian,Alexandre Chabrol,Frédéric Wallyn,Leonardo Magro,Flore Sicre de Fontbrune,Regis Peffault de la Tour,Abdellatif Tazi,Amira Benattia,Remi Valter,Philippe Devillier,Louis-Jean Couderc,Felipe Suarez,Emilie Catherinot,Hélène Salvator
{"title":"The impact of allogeneic hematopoietic stem cell transplantation on pulmonary complications in adults with inborn errors of immunity.","authors":"Aurélie Le Gal,Ambroise Marcais,Céline Goyard,Anne-Laure Brun,Morgane Cheminant,Nizar Mahlaoui,Claire Givel,Colas Tcherakian,Alexandre Chabrol,Frédéric Wallyn,Leonardo Magro,Flore Sicre de Fontbrune,Regis Peffault de la Tour,Abdellatif Tazi,Amira Benattia,Remi Valter,Philippe Devillier,Louis-Jean Couderc,Felipe Suarez,Emilie Catherinot,Hélène Salvator","doi":"10.1016/j.jaci.2025.04.032","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.032","url":null,"abstract":"BACKGROUNDPulmonary involvement (repeated lung infections, lung parenchymal inflammation, scarring, and malignancies) is frequent in patients with inborn errors of immunity (IEI) and accounts for a significant proportion of the disease burden. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure most severe IEI. The indications for allo-HSCT have recently been extended to adults.OBJECTIVEWe sought to assess the impact of allo-HSCT specifically on respiratory status METHODS: We retrospectively analyzed data on 50 patients with IEI who underwent a first allo-HSCT after the age of 16 at three expert centers in France.RESULTSThe median [interquartile range] length of follow-up was 4.8 years [IQR: 1.6;9.2] before allo-HSCT and 3 years [1.4;6.0] afterwards. Ten patients died from allo-HSCT-related complications. Four patients developed bronchiolitis obliterans syndrome. After the first-year post-transplantation, the mean annualized rate of severe respiratory infections (0.14 (95%CI: 0.04;0.24)) was lower than the value recorded before transplantation (0.54 (95%CI: 0.25;0.82); p=0.003 for paired comparisons of equivalent durations). Lung function was declining before allo-HSCT (mean (95%CI) FEV1: -2.09 %predicted/year (-7.27;3.09)] but increased afterwards (+2.44 %predicted/year (-4.79;9.69), p=0.0034 for paired comparisons). On CT scans of the chest, bronchial disorders and lung parenchyma cavities were the most frequent abnormal findings. The bronchial thickening and bronchiolar micronodules regressed after allo-HSCT, while bronchiectasis and residual parenchymal cavities were stable.CONCLUSIONAllo-HSCT appears likely to protect the long-term pulmonary prognosis of adults with IEI; it is associated with a significantly lower incidence of severe respiratory infections, better lung function, and the radiological stabilization of lung damage.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"14 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083366","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}
引用次数: 0
Expansion of multiple CD4+ T cell lineages in lymphocytic variant hypereosinophilic syndrome. 淋巴细胞变异型嗜酸性粒细胞增多综合征中多个CD4+ T细胞系的扩增。
IF 14.2 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-09 DOI: 10.1016/j.jaci.2025.04.027
Charles F Anderson,Michelle Makiya,Knaunong Xiong,Lori Penrod,Lauren Wetzler,JeanAnne Ware,Greg Constantine,Paneez Khoury,Amy D Klion
{"title":"Expansion of multiple CD4+ T cell lineages in lymphocytic variant hypereosinophilic syndrome.","authors":"Charles F Anderson,Michelle Makiya,Knaunong Xiong,Lori Penrod,Lauren Wetzler,JeanAnne Ware,Greg Constantine,Paneez Khoury,Amy D Klion","doi":"10.1016/j.jaci.2025.04.027","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.027","url":null,"abstract":"BACKGROUNDLymphocytic variant hypereosinophilic syndrome (LHES) is a rare disorder characterized by hypereosinophilia, the presence of phenotypically aberrant populations of Th2 lymphocytes and varied clinical manifestations. Although disease pathogenesis has historically been attributed to IL-5 driven hypereosinophilia, response to eosinophil-lowering biologics is not universal, suggesting a more direct role for the aberrant lymphocyte population in disease pathogenesis.OBJECTIVETo further delineate the surface phenotypes and cytokine profiles of the aberrant lymphocyte populations in patients with LHES METHODS: Multiparameter flow cytometry was used to analyze lymphocytes in whole blood and stored peripheral blood mononuclear cells from a cohort of 42 untreated and treated patients with LHES.RESULTSSurface receptor profiling of the aberrant population in 22 untreated patients with LHES, including 8 patients with episodic angioedema with eosinophilia (EAE), confirmed prior data demonstrating that the aberrant CD4+ T cell populations in LHES have a Th2 memory phenotype. CCR8 was identified as a dominant surface marker, unaffected by sample processing or patient treatment status. Serum levels of CCL1, the ligand for CCR8 were increased in LHES patients compared to patients with other HES subtypes. Expanded populations of Foxp3+Helios+CCR8+ regulatory T cells were identified in many patients with CD3loCD4+ LHES and correlated with the size of the CD3loCD4+ population.CONCLUSIONThese data provide further evidence for direct involvement of the aberrant T cell populations in disease pathogenesis in LHES and a rationale for further exploration of T cell-directed therapies.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"26 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932739","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}
引用次数: 0
Dupilumab-induced inhibition of myeloid dendritic cells function via TIM-3-TGF-β1 feedback loop in treatment of atopic dermatitis. dupilumab诱导的通过TIM-3-TGF-β1反馈回路抑制骨髓树突状细胞功能治疗特应性皮炎。
IF 14.2 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-08 DOI: 10.1016/j.jaci.2025.05.001
Yishan Chen,Yuyang Tian,Siqi Liu,Kefan Lin,Rong Tao,Bocheng Wang,Yijia Ruan,Mingjun Hou,Di Wang,Yurong Luo,Chunyan Li,Puyu Zou,Yunsheng Liang,Pan Lai,Danchen Hu,Weiwei Deng
{"title":"Dupilumab-induced inhibition of myeloid dendritic cells function via TIM-3-TGF-β1 feedback loop in treatment of atopic dermatitis.","authors":"Yishan Chen,Yuyang Tian,Siqi Liu,Kefan Lin,Rong Tao,Bocheng Wang,Yijia Ruan,Mingjun Hou,Di Wang,Yurong Luo,Chunyan Li,Puyu Zou,Yunsheng Liang,Pan Lai,Danchen Hu,Weiwei Deng","doi":"10.1016/j.jaci.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.05.001","url":null,"abstract":"BACKGROUNDAlthough clinical trials have demonstrated both the efficacy and safety of dupilumab, its impact on dendritic cells (DCs) remains unclear. TIM-3 has emerged as crucial regulators of immune responses in various inflammatory diseases. Understanding the interplay between TIM-3 and the type 2 inflammatory response in atopic dermatitis (AD) could provide valuable insights into the mechanisms underlying the efficacy of dupilumab.OBJECTIVETo investigate whether TIM-3 induce immune modulation of DCs and determine its role in dupilumab therapy.METHODSUsing single-cell technology to screen for the expression landscape of immune checkpoints. Employing αIL-4/IL-13 monoclonal antibody treatment in mice to simulate the therapeutic effects of dupilumab treatment. Investigating the function of the immune checkpoint Tim-3 with αTim-3 monoclonal antibody. Finally, peripheral blood mononuclear cells (PBMCs) were collected from AD patients 16 weeks before and after dupilumab treatment (n=24) to validate the findings observed in the mouse experiments. Additionally, AD skin lesions were collected before treatment (n=8) and after treatment (n=5) for further validation. To verify the therapeutic effects of TGF-β1 and Galectin-9, we also collected PBMCs from untreated AD patients (n=21) and conducted in vitro stimulation experiments.RESULTSDupilumab upregulates the immune checkpoint HAVCR2 (encoding TIM-3) by inducing the secretion of TGF-β1 in myeloid DCs. Interestingly, TIM-3 also promotes the secretion of TGF-β1, thus forming a positive feedback loop. This process was found to promote myeloid DC apoptosis, contributing to the observed decrease in myeloid DC numbers and potentially enhancing the therapeutic effects of dupilumab. The analyses of PBMCs and skin lesions from AD patients before and after dupilumab treatment showed dupilumab significantly elevated the levels of TIM-3, which correlated with a reduced proportion of myeloid DCs and suppressed myeloid DC function. In vitro stimulation of PBMCs with TGF-β1 or Galectin-9 similarly revealed their ability to inhibit myeloid DCs function in AD, suggesting potential therapeutic effects.CONCLUSIONDupilumab improves the symptoms of AD by inducing the expression of TIM-3 to suppress myeloid DCs function, treatment with the TGF-β1 or Galectin-9 enhanced these effects, demonstrating the therapeutic potential of targeting the TGF-β1/ Galectin-9-TIM-3 axis in AD.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"21 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932740","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}
引用次数: 0
Eosinophilic Esophagitis (EoE): Allergy & Immunology Perspective on the Updated Guidelines. 嗜酸性粒细胞性食管炎(EoE):最新指南的过敏和免疫学观点。
IF 14.2 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-06 DOI: 10.1016/j.jaci.2025.04.026
Emily C McGowan,Benjamin L Wright,Melanie A Ruffner,Robert D Pesek,Marc E Rothenberg,Jonathan M Spergel,Evan S Dellon,Seema S Aceves
{"title":"Eosinophilic Esophagitis (EoE): Allergy & Immunology Perspective on the Updated Guidelines.","authors":"Emily C McGowan,Benjamin L Wright,Melanie A Ruffner,Robert D Pesek,Marc E Rothenberg,Jonathan M Spergel,Evan S Dellon,Seema S Aceves","doi":"10.1016/j.jaci.2025.04.026","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.026","url":null,"abstract":"In January 2025, the American College of Gastroenterology (ACG) published updated guidelines on the diagnosis and management of eosinophilic esophagitis (EoE). These new guidelines incorporated updated information on the pathophysiology, risk factors, natural history, and treatment of EoE. As these guidelines were primarily intended for practicing gastroenterologists, this Paradigm and Perspectives article summarizes the key recommendations for the Allergy & Immunology community. In addition, as the prevalence and healthcare burden of EoE continues to increase, the population affected is primarily allergic individuals, and less-invasive monitoring techniques are on the horizon, we discuss the key means by which allergists can contribute to the diagnosis and management of EoE. In particular, allergists can participate in screening for subtle EoE symptoms among their allergy patients, assist in optimizing the management of other allergic comorbidities, provide education about elimination diets, and facilitate the monitoring of disease over time. Allergists are uniquely poised to treat the entire allergic individual, rather than just the allergic esophagus, and should be prepared to co-manage these patients with gastroenterologists.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"58 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926381","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}
引用次数: 0
The DBS proteome identifies a subclinical IFN signature in neonates with type I interferonopathy. DBS蛋白质组鉴定了I型干扰素病新生儿的亚临床IFN特征。
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-02 DOI: 10.1016/j.jaci.2025.04.025
Hiroshi Nihira, Daisuke Nakajima, Kazushi Izawa, Yusuke Kawashima, Hirofumi Shibata, Ryo Konno, Motoko Higashiguchi, Takayuki Miyamoto, Masahiko Nishitani-Isa, Eitaro Hiejima, Yoshitaka Honda, Tadashi Matsubayashi, Takashi Ishihara, Masato Yashiro, Naomi Iwata, Yoko Ohwada, Seiichi Tomotaki, Masahiko Kawai, Kosaku Murakami, Hidenori Ohnishi, Masataka Ishimura, Satoshi Okada, Motoi Yamashita, Tomohiro Morio, Akihiro Hoshino, Hirokazu Kanegane, Kohsuke Imai, Yasuko Nakamura, Shigeaki Nonoyama, Toru Uchiyama, Masafumi Onodera, Takashi Ishikawa, Toshinao Kawai, Junko Takita, Ryuta Nishikomori, Osamu Ohara, Takahiro Yasumi
{"title":"The DBS proteome identifies a subclinical IFN signature in neonates with type I interferonopathy.","authors":"Hiroshi Nihira, Daisuke Nakajima, Kazushi Izawa, Yusuke Kawashima, Hirofumi Shibata, Ryo Konno, Motoko Higashiguchi, Takayuki Miyamoto, Masahiko Nishitani-Isa, Eitaro Hiejima, Yoshitaka Honda, Tadashi Matsubayashi, Takashi Ishihara, Masato Yashiro, Naomi Iwata, Yoko Ohwada, Seiichi Tomotaki, Masahiko Kawai, Kosaku Murakami, Hidenori Ohnishi, Masataka Ishimura, Satoshi Okada, Motoi Yamashita, Tomohiro Morio, Akihiro Hoshino, Hirokazu Kanegane, Kohsuke Imai, Yasuko Nakamura, Shigeaki Nonoyama, Toru Uchiyama, Masafumi Onodera, Takashi Ishikawa, Toshinao Kawai, Junko Takita, Ryuta Nishikomori, Osamu Ohara, Takahiro Yasumi","doi":"10.1016/j.jaci.2025.04.025","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.025","url":null,"abstract":"<p><strong>Background: </strong>Type I interferonopathy is characterized by aberrant upregulation of type I interferon (IFN) signaling. The mRNA-IFN signature is a useful marker for activation of the IFN pathway, and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.</p><p><strong>Objective: </strong>This study sought to identify the proteomic IFN signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the IFN signature for neonatal screening, and to gain insight into pre-symptomatic state of neonates with inborn errors of immunity (IEIs).</p><p><strong>Methods: </strong>DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs, and from neonates with viral infections, including some samples obtained during the pre-symptomatic neonatal period, were examined by non-targeted proteome analyses. Expression of IFN-stimulated genes (ISGs) was evaluated and a DBS-IFN signature was defined. Differential expression/pathway analysis were also performed.</p><p><strong>Results: </strong>ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z-scores for these as the DBS-IFN signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high IFN signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus-like pathways.</p><p><strong>Conclusion: </strong>Upregulation of the IFN pathway exists already at birth not only in neonates with type I interferonopathy but also with other IEIs, including CGD.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004746","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}
引用次数: 0
First description of familial hypertryptasemia 首次描述家族性高血脂症。
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-05-01 DOI: 10.1016/j.jaci.2025.01.041
Ignacio Dávila MD, PhD , Laura Hernández-Hernández BsC, PhD , Felix Lorente-Toledano MD, PhD , Catalina Sanz BsC, PhD , María Isidoro-García MD, PhD
{"title":"First description of familial hypertryptasemia","authors":"Ignacio Dávila MD, PhD ,&nbsp;Laura Hernández-Hernández BsC, PhD ,&nbsp;Felix Lorente-Toledano MD, PhD ,&nbsp;Catalina Sanz BsC, PhD ,&nbsp;María Isidoro-García MD, PhD","doi":"10.1016/j.jaci.2025.01.041","DOIUrl":"10.1016/j.jaci.2025.01.041","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1684-1685"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567164","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}
引用次数: 0
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