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YTHDF1 regulates the proliferation and differentiation of keratinocytes via the PI3K/AKT signaling pathway in atopic dermatitis 在特应性皮炎中,YTHDF1通过PI3K/AKT信号通路调控角质形成细胞的增殖和分化。
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.04.005
Maoxin Huang , Liping Dong , Yue He , Xinying Cai , Yun Lu , Jinlei Xu , Fengli Xiao

Background

YTHDF1, a critical regulator of cellular processes, has attracted attention for its involvement in some inflammatory diseases. However, its specific association with atopic dermatitis (AD) remains unclear. The objective is to investigate the functional roles and underlying mechanisms of YTHDF1 in AD.

Methods

The expression of YTHDF1 was investigated by bioinformatics analysis and skin lesions of AD patients. The functional role and upstream and downstream regulatory mechanisms of YTHDF1 were examined through a series of in vitro and in vivo experiments. Adeno-associated virus (AAV)-mediated delivery of YTHDF1 in the AD mouse model was evaluated for its therapeutic potential.

Results

Bioinformatics analysis revealed that the YTHDF1 mRNA level in the skin lesions of AD was significantly higher than that in healthy people. YTHDF1 expression was significantly elevated in AD skin lesions, the DNCB-induced AD mouse model, and primary human keratinocytes and HaCaT cells stimulated with interleukin (IL)-4/IL-13, compared to controls. Both in vitro and in vivo experiments revealed that upregulation of YTHDF1 in AD exacerbated cell proliferation and inhibited keratinization by activating the PI3K/AKT pathway, which was modulated via the IL-4/IL-13/STAT3 axis. Moreover, topical application of AAV-YTHDF1 significantly improved AD-like lesions in the mouse model.

Conclusions

This study identifies YTHDF1 as a contributor to AD pathogenesis by influencing keratinocyte proliferation and differentiation. It also suggests that YTHDF1 could be a potential therapeutic target for AD treatment.
背景:YTHDF1是细胞过程的关键调节因子,因其参与一些炎症性疾病而受到关注。然而,其与特应性皮炎(AD)的具体关系尚不清楚。目的是研究YTHDF1在AD中的功能作用和潜在机制。方法:通过生物信息学分析和AD患者皮肤病变情况研究YTHDF1的表达。通过一系列体外和体内实验,研究了YTHDF1的功能作用和上下游调控机制。腺相关病毒(AAV)介导的YTHDF1在AD小鼠模型中的传递被评估其治疗潜力。结果:生物信息学分析显示,AD皮损组织中YTHDF1 mRNA水平明显高于健康人。与对照组相比,YTHDF1在AD皮损、dncb诱导的AD小鼠模型以及白细胞介素(IL)-4/IL-13刺激的人原代角质形成细胞和HaCaT细胞中的表达显著升高。体外和体内实验均表明,在AD中上调YTHDF1可通过激活PI3K/AKT通路(通过IL-4/IL-13/STAT3轴调节),从而加剧细胞增殖并抑制角化。此外,局部应用AAV-YTHDF1可显著改善小鼠模型ad样病变。结论:本研究确定YTHDF1通过影响角质细胞增殖和分化参与AD的发病机制。这也表明YTHDF1可能是阿尔茨海默病治疗的潜在治疗靶点。
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引用次数: 0
Factors associated with egg aversion after a negative oral food challenge result in children with egg allergies: A multicenter questionnaire survey in Japan 在日本进行的一项多中心问卷调查显示,在负面的口腔食物挑战后,与鸡蛋厌恶相关的因素导致了儿童鸡蛋过敏。
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.05.005
Naoko Fusayasu , Tomoyuki Asaumi , Ken-Ichi Nagakura , Kyohei Takahashi , Noriyuki Yanagida , Sakura Sato , Shigehito Emura , Akiko Murano , Hisashi Konno , Yasuko Shibukawa , Makoto Suzuki , Motohiro Ebisawa

Background

Many children with egg allergies experience aversion, which hinders reintroduction after a negative oral food challenge (OFC). We aimed to assess factors associated with egg aversion in children after negative egg OFCs.

Methods

We conducted a multicenter questionnaire survey between January and December 2018 and retrospectively collected background data from the medical records. Children aged 3–18 years with a history of an immediate reaction to eggs more than 6 months after a negative OFC to half of a heated whole egg were included. We defined “aversion” as a dislike of eating eggs or processed egg products.

Results

We included 140 children (median age: 6.7 years) who passed OFCs at the median age of 3.3 years and had a median specific-IgE (sIgE) to egg white of 10.0 kUA/L. Overall, 57 (41 %) children had an egg aversion. “Disliking the food texture or taste” (61 %) was the most frequent reason for an aversion. The associated factor in the multivariate analysis was older age during a negative OFC (adjusted odds ratio: 1.24, 95 % confidence interval: 1.04–1.49). The aversion frequency depended on the type of cooking methods, where 68 % had an aversion to boiled egg whites, and less than 5 % had an aversion to egg-containing deep-fried chicken.

Conclusions

About half of the children after negative OFC had an egg aversion, and it was associated with older age during negative OFC. Careful follow-up and guidance with consideration of less aversive cooking methods are important in older age groups.
背景:许多有鸡蛋过敏的儿童经历厌恶,这阻碍了口服食物挑战(OFC)后的重新引入。我们的目的是评估卵子OFCs阴性后儿童厌恶鸡蛋的相关因素。方法:于2018年1月至12月进行多中心问卷调查,回顾性收集病历背景资料。研究对象为3-18岁的儿童,在对半个加热的全蛋的OFC呈阴性反应超过6个月后,对鸡蛋有立即反应史。我们将“厌恶”定义为不喜欢吃鸡蛋或加工过的蛋制品。结果:我们纳入了140名儿童(中位年龄:6.7岁),他们在中位年龄3.3岁时通过OFCs,中位蛋白特异性ige (sIgE)为10.0 kUA/L。总体而言,57名(41%)儿童厌恶鸡蛋。“不喜欢食物的质地或味道”(61%)是最常见的厌恶原因。多变量分析中的相关因素是OFC阴性时的年龄较大(校正优势比:1.24,95%可信区间:1.04-1.49)。厌恶的频率取决于烹饪方法的类型,其中68%的人讨厌煮蛋清,不到5%的人讨厌含鸡蛋的炸鸡。结论:OFC阴性后约有一半的儿童厌恶鸡蛋,并且与OFC阴性期间的年龄有关。仔细的后续行动和指导,考虑较少令人厌恶的烹饪方法,对老年群体很重要。
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引用次数: 0
Black-box optimization in immunology and beyond: A practical guide to algorithms and future directions 黑箱优化在免疫学和超越:算法和未来方向的实用指南。
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.08.006
Takanori Kawabata , Taku Tsuzuki , Tsuyoshi Tatsukawa , Kota Matsui , Eiryo Kawakami
The immune system presents some of the most complex challenges in biology, encompassing nonlinear interactions, high-dimensional regulatory mechanisms, and substantial variability across individuals and contexts. As a result, traditional model-driven approaches often fall short in optimizing experimental conditions or therapeutic strategies. Black-box optimization methods—particularly Bayesian optimization (BO) and evolutionary algorithms (EAs)—offer powerful tools for guiding biological discovery when mechanistic understanding is incomplete or intractable. These algorithms iteratively propose informative experiments by learning from noisy, expensive, and sparse data, enabling efficient exploration of vast experimental spaces. In this review, we provide a comprehensive overview of black-box optimization methodologies and their applications in life science, with a particular focus on immunology and allergy research. We detail how black-box optimization is transforming various stages of biomedical R&D, from molecular design (e.g., antibodies, peptides) and gene circuit tuning to culture protocol optimization and patient-specific dose adjustment. We highlight key algorithmic advances, including constrained, multi-objective, parallel and high-dimensional BO, as well as recent developments such as grey-box optimization and transfer learning. Practical considerations, such as software tools and reproducibility-enhancing checklists, are also discussed. By integrating black-box optimization with automated experimentation platforms and high-throughput biological systems, researchers can accelerate discovery, personalize interventions, and systematically optimize complex immunological processes. We argue that black-box optimization will become a foundational component of experimental design and decision-making in the life sciences, bridging computational strategies with biological insight in increasingly adaptive and interpretable ways.
免疫系统是生物学中一些最复杂的挑战,包括非线性相互作用,高维调节机制,以及个体和环境之间的巨大差异。因此,传统的模型驱动方法在优化实验条件或治疗策略方面往往存在不足。黑箱优化方法——尤其是贝叶斯优化(BO)和进化算法(ea)——在机制理解不完整或难以理解的情况下,为指导生物发现提供了强大的工具。这些算法通过从嘈杂、昂贵和稀疏的数据中学习,迭代地提出信息丰富的实验,从而能够有效地探索广阔的实验空间。本文综述了黑盒优化方法及其在生命科学中的应用,重点介绍了免疫学和过敏症研究。我们详细介绍了黑盒优化如何改变生物医学研发的各个阶段,从分子设计(例如,抗体,肽)和基因电路调整到培养方案优化和患者特异性剂量调整。我们强调了关键的算法进展,包括约束、多目标、并行和高维BO,以及最近的发展,如灰盒优化和迁移学习。还讨论了实际考虑因素,例如软件工具和增强再现性的检查表。通过将黑盒优化与自动化实验平台和高通量生物系统集成,研究人员可以加速发现,个性化干预,并系统地优化复杂的免疫过程。我们认为,黑箱优化将成为生命科学实验设计和决策的基础组成部分,以越来越适应和可解释的方式将计算策略与生物洞察力联系起来。
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引用次数: 0
Artificial intelligence and big data: Reshaping allergy research and patient care 人工智能和大数据:重塑过敏研究和患者护理
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.09.001
Eiryo Kawakami (Guest Editor, Allergology International)
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引用次数: 0
The role of GATA2 in the expression of the soluble decoy receptor ST2/IL1RL1 in human and mouse mast cells GATA2在人和小鼠肥大细胞中可溶性诱骗受体ST2/IL1RL1表达中的作用
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.04.004
Kazuki Nagata , Kazumi Kasakura , Kenta Ishii , Naoto Ito , Mutsuko Hara , Nobuhiro Nakano , Ko Okumura , Chiharu Nishiyama
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引用次数: 0
Convergent monoclonal IgE antibodies from peanut allergic patients are multispecific to immunodominant epitopes of unrelated major peanut and tree nut allergens 来自花生过敏患者的收敛性单克隆IgE抗体对不相关的主要花生和树坚果过敏原的免疫显性表位具有多特异性。
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.05.007
Stefan Kabasser , Tanja Kalic Kamath , Ernst Eber , Aleksandra Podzhilkova , Christian Lupinek , Wolfgang Hemmer , Mugdim Bublin , Derek Croote , Soheila J. Maleki , Heimo Breiteneder , Karin Hoffmann-Sommergruber , Christian Radauer , Merima Bublin

Background

Convergent selection has been identified in the IgE antibody repertoires of peanut-allergic individuals, primarily targeting the 2S albumin Ara h 2 and cross-reacting with two other major allergens, the vicilin Ara h 1 and the legumin Ara h 3. In this study, we aimed to investigate the structural and functional basis of this cross-reactivity and its contribution to the co-sensitization to tree nuts often observed in peanut-allergic subjects.

Methods

Six convergent antibodies, targeting the immunodominant Ara h 2-DPYSPS motif-associated sequence, and their reverted germline version, were produced as human IgG1 and IgE. Antibody specificity to natural and recombinant peanut and tree nut allergens and allergen-derived peptides was evaluated using ELISA, immunoblotting, inhibition tests, and basophil activation assays.

Results

The six antibodies showed reactivity to Ara h 1, Ara h 2, Ara h 3 and weak reactivity to tree nut legumins, especially from almond, walnut and Brazil nut. The germline antibody exclusively recognized Ara h 2. Basophils sensitized with the individual antibodies were activated by Ara h 2 at a concentration of 10 ng/ml and at 100-fold higher concentrations by Ara h 1 and Ara h 3, but not by tree nut legumins. The three Ara h 1- and two Ara h 3-derived antibody-binding peptides, with one from each group previously identified as immunodominant, are in close proximity and may contribute to conformational epitopes.

Conclusion

The biological activity of affinity-matured cross-reactive antibodies with Ara h 2-associated sequence convergence may explain the high allergenic potency of peanut and clinically irrelevant co-sensitizations to tree nuts commonly observed in peanut-allergic patients.
背景:在花生过敏个体的IgE抗体谱中发现了趋同选择,主要针对2S白蛋白Ara h2,并与另外两种主要过敏原,蛔虫蛋白Ara h1和豆类蛋白Ara h3交叉反应。在这项研究中,我们旨在研究这种交叉反应的结构和功能基础,以及它在花生过敏受试者中经常观察到的对树坚果的共致敏中的贡献。方法:制备6种针对Ara h 2-DPYSPS基序相关序列的趋同抗体,并将其还原为人IgG1和IgE。采用ELISA、免疫印迹、抑制试验和嗜碱性粒细胞活化试验评估对天然和重组花生和树坚果过敏原和过敏原衍生肽的抗体特异性。结果:6种抗体对arah1、arah2、arah3具有反应性,对树坚果类豆类蛋白的反应性较弱,尤其是杏仁、核桃和巴西坚果。种系抗体只识别Ara h2。被单个抗体致敏的嗜碱性细胞被浓度为10 ng/ml的Ara h2激活,Ara h1和Ara h3的浓度比Ara h2高100倍,但不被树坚果豆类蛋白激活。三个Ara h - 1和两个Ara h - 3衍生的抗体结合肽,每一组中有一个先前被确定为免疫优势,它们非常接近,可能有助于构象表位。结论:具有Ara h 2相关序列趋同的亲和成熟交叉反应抗体的生物学活性可能解释了花生高致敏效力和花生过敏患者常见的对树坚果的临床不相关的共致敏。
{"title":"Convergent monoclonal IgE antibodies from peanut allergic patients are multispecific to immunodominant epitopes of unrelated major peanut and tree nut allergens","authors":"Stefan Kabasser ,&nbsp;Tanja Kalic Kamath ,&nbsp;Ernst Eber ,&nbsp;Aleksandra Podzhilkova ,&nbsp;Christian Lupinek ,&nbsp;Wolfgang Hemmer ,&nbsp;Mugdim Bublin ,&nbsp;Derek Croote ,&nbsp;Soheila J. Maleki ,&nbsp;Heimo Breiteneder ,&nbsp;Karin Hoffmann-Sommergruber ,&nbsp;Christian Radauer ,&nbsp;Merima Bublin","doi":"10.1016/j.alit.2025.05.007","DOIUrl":"10.1016/j.alit.2025.05.007","url":null,"abstract":"<div><h3>Background</h3><div>Convergent selection has been identified in the IgE antibody repertoires of peanut-allergic individuals, primarily targeting the 2S albumin Ara h 2 and cross-reacting with two other major allergens, the vicilin Ara h 1 and the legumin Ara h 3. In this study, we aimed to investigate the structural and functional basis of this cross-reactivity and its contribution to the co-sensitization to tree nuts often observed in peanut-allergic subjects.</div></div><div><h3>Methods</h3><div>Six convergent antibodies, targeting the immunodominant Ara h 2-DPYSPS motif-associated sequence, and their reverted germline version, were produced as human IgG1 and IgE. Antibody specificity to natural and recombinant peanut and tree nut allergens and allergen-derived peptides was evaluated using ELISA, immunoblotting, inhibition tests, and basophil activation assays.</div></div><div><h3>Results</h3><div>The six antibodies showed reactivity to Ara h 1, Ara h 2, Ara h 3 and weak reactivity to tree nut legumins, especially from almond, walnut and Brazil nut. The germline antibody exclusively recognized Ara h 2. Basophils sensitized with the individual antibodies were activated by Ara h 2 at a concentration of 10 ng/ml and at 100-fold higher concentrations by Ara h 1 and Ara h 3, but not by tree nut legumins. The three Ara h 1- and two Ara h 3-derived antibody-binding peptides, with one from each group previously identified as immunodominant, are in close proximity and may contribute to conformational epitopes.</div></div><div><h3>Conclusion</h3><div>The biological activity of affinity-matured cross-reactive antibodies with Ara h 2-associated sequence convergence may explain the high allergenic potency of peanut and clinically irrelevant co-sensitizations to tree nuts commonly observed in peanut-allergic patients.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 622-632"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486739","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}
引用次数: 0
Artificial intelligence in clinical data analysis: A review of large language models, foundation models, digital twins, and allergy applications 临床数据分析中的人工智能:大型语言模型、基础模型、数字双胞胎和过敏应用综述。
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.06.005
Yutaro Fuse , Shawn N. Murphy , Hisahiro Ikari , Akiko Takahashi , Kenshiro Fuse , Eiryo Kawakami
Recent advances in computing technology and the development of data utilization environments have rapidly accelerated the application of artificial intelligence in clinical research and healthcare. This review provides a comprehensive overview of current machine learning techniques for analyzing clinical data, with illustrative examples from the field of allergic diseases. In addition to conventional methods for clinical data analysis, we discuss emerging approaches including medical image analysis and time-series modeling of electronic health record data. Recent developments such as large language models and foundation models trained on massive datasets are also discussed. Looking ahead, we explore future directions in analytical methodology, including mathematical modeling, interpretable artificial intelligence, and multimodal learning that integrates various data types. We also introduce the concept of the digital twin—a virtual representation of an individual patient that simulates disease progression and treatment response—as a promising concept for advancing precision medicine. Finally, we discuss the essential role of physicians in the development and implementation of machine learning tools and discuss emerging ethical issues such as fairness, privacy, and patient autonomy. By synthesizing recent technical advances with clinical relevance, this review aims to provide clinicians and researchers with a practical and forward-looking guide to machine learning in clinical medicine, including its growing application in the field of allergy.
最近计算技术的进步和数据利用环境的发展迅速加速了人工智能在临床研究和医疗保健中的应用。本文综述了当前用于分析临床数据的机器学习技术的全面概述,并提供了过敏性疾病领域的说明性示例。除了传统的临床数据分析方法外,我们还讨论了新兴的方法,包括医学图像分析和电子健康记录数据的时间序列建模。最近的发展,如大型语言模型和基础模型训练的大规模数据集也进行了讨论。展望未来,我们将探索分析方法的未来方向,包括数学建模、可解释的人工智能和集成各种数据类型的多模态学习。我们还介绍了数字孪生的概念——模拟疾病进展和治疗反应的单个患者的虚拟表示——作为推进精准医学的一个有前途的概念。最后,我们讨论了医生在机器学习工具的开发和实施中的重要作用,并讨论了诸如公平、隐私和患者自主权等新兴伦理问题。通过综合近期与临床相关的技术进展,本综述旨在为临床医生和研究人员提供实用和前瞻性的临床医学机器学习指南,包括其在过敏领域的日益增长的应用。
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引用次数: 0
Establishment of a novel human basophil cell line for functional analysis and in vitro allergy testing 一种用于功能分析和体外过敏试验的新型人嗜碱性细胞系的建立。
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.03.003
Ryo Kurita, Takaaki Abe, Kanako Maebara, Daisuke Takahashi, Shigeki Miyata, Masahiro Satake, Yoshihiko Tani

Background

Basophils are the rarest granulocytes and play diverse roles, e.g., in protective immunity and allergic inflammatory reactions. However, the underlying molecules and mechanisms involved in basophil differentiation and functions, particularly in humans, remain largely unknown. This may be due to the lack of high-quality research tools.

Methods

We established a novel, immortalized, human basophil cell line by introducing human papillomavirus 16-E6/E7, c-MYC, and BCL-xL gene expression systems into cultured basophils, and evaluated whether this cell line is useful as a research tool, compared with KU812, which is the most commonly-used human basophil cell line.

Results

This cell line expressed various basophil markers, including CD123, CD203c, and the high-affinity immunoglobulin (Ig)E receptor α-chain and can mature into more differentiated cells under specific culture conditions. The differentiated cells stimulated with anti-IgE antibodies showed increased CD203c expression in a dose-dependent manner, whereas the differentiated KU812 cells showed little activation after the stimulation.
The established cell line also demonstrated increased sensitivity to allergic activation when stimulated with an allergen (NP-BSA) and allergen-specific IgE (anti-NP-IgE). Furthermore, histamine- and interleukin-4-releasing abilities were also confirmed. These allergic activation profiles were similar to those of basophils from healthy individuals, although the activation levels of the established cells were lower than those of basophils from highly-sensitive individuals.

Conclusions

These findings suggest that the established basophil cell line has substantially different characteristics from a conventional cell line and could serve as a new tool for investigating basophil differentiation and functions, as well as for testing allergic reactions.
背景:嗜碱性粒细胞是最罕见的粒细胞,在保护性免疫和过敏性炎症反应中发挥着多种作用。然而,涉及嗜碱性粒细胞分化和功能的潜在分子和机制,特别是在人类中,仍然很大程度上未知。这可能是由于缺乏高质量的研究工具。方法:将人乳头瘤病毒16-E6/E7、c-MYC和BCL-xL基因表达系统导入培养的嗜碱性细胞中,建立一种新的永生化人嗜碱性细胞系,并与最常用的人嗜碱性细胞系KU812进行比较,评估该细胞系是否可作为研究工具。结果:该细胞系表达CD123、CD203c及高亲和性免疫球蛋白E受体α-链等多种嗜碱性细胞标志物,在特定培养条件下可成熟为分化程度较高的细胞。经抗ige抗体刺激的分化细胞CD203c表达呈剂量依赖性增加,而KU812细胞在刺激后几乎没有活化。当用过敏原(NP-BSA)和过敏原特异性IgE(抗np -IgE)刺激时,所建立的细胞系也显示出对过敏激活的敏感性增加。此外,组胺和白细胞介素-4的释放能力也得到证实。这些过敏激活谱与来自健康个体的嗜碱性细胞相似,尽管建立的细胞的激活水平低于来自高度敏感个体的嗜碱性细胞。结论:这些发现表明,所建立的嗜碱性粒细胞细胞系具有与常规细胞系截然不同的特征,可以作为研究嗜碱性粒细胞分化和功能以及检测过敏反应的新工具。
{"title":"Establishment of a novel human basophil cell line for functional analysis and in vitro allergy testing","authors":"Ryo Kurita,&nbsp;Takaaki Abe,&nbsp;Kanako Maebara,&nbsp;Daisuke Takahashi,&nbsp;Shigeki Miyata,&nbsp;Masahiro Satake,&nbsp;Yoshihiko Tani","doi":"10.1016/j.alit.2025.03.003","DOIUrl":"10.1016/j.alit.2025.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Basophils are the rarest granulocytes and play diverse roles, e.g., in protective immunity and allergic inflammatory reactions. However, the underlying molecules and mechanisms involved in basophil differentiation and functions, particularly in humans, remain largely unknown. This may be due to the lack of high-quality research tools.</div></div><div><h3>Methods</h3><div>We established a novel, immortalized, human basophil cell line by introducing human papillomavirus 16-E6<em>/</em>E7, <em>c-MYC</em>, and <em>BCL-xL</em> gene expression systems into cultured basophils, and evaluated whether this cell line is useful as a research tool, compared with KU812, which is the most commonly-used human basophil cell line.</div></div><div><h3>Results</h3><div>This cell line expressed various basophil markers, including CD123, CD203c, and the high-affinity immunoglobulin (Ig)E receptor α-chain and can mature into more differentiated cells under specific culture conditions. The differentiated cells stimulated with anti-IgE antibodies showed increased CD203c expression in a dose-dependent manner, whereas the differentiated KU812 cells showed little activation after the stimulation.</div><div>The established cell line also demonstrated increased sensitivity to allergic activation when stimulated with an allergen (NP-BSA) and allergen-specific IgE (anti-NP-IgE). Furthermore, histamine- and interleukin-4-releasing abilities were also confirmed. These allergic activation profiles were similar to those of basophils from healthy individuals, although the activation levels of the established cells were lower than those of basophils from highly-sensitive individuals.</div></div><div><h3>Conclusions</h3><div>These findings suggest that the established basophil cell line has substantially different characteristics from a conventional cell line and could serve as a new tool for investigating basophil differentiation and functions, as well as for testing allergic reactions.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 579-590"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789107","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}
引用次数: 0
Improvement of atopic dermatitis-like symptoms in a murine model via the chromogranin A-derived peptide catestatin 通过嗜铬粒蛋白a衍生肽catestatin改善小鼠模型中的特应性皮炎样症状。
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.01.001
Ge Peng , Wanchen Zhao , Alafate Abudouwanli , Quan Sun , Mengyao Yang , Shan Wang , Yi Tan , Arisa Ikeda , Shigaku Ikeda , Hideoki Ogawa , Ko Okumura , François Niyonsaba

Background

Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is characterized by compromised skin barrier and heightened immune responses. The study investigates the therapeutic efficacy of catestatin (CST), a chromogranin A-derived antimicrobial peptide, in mitigating AD-like symptoms.

Methods

Utilizing both keratinocyte cultures and a C57BL/6 mouse model, we examined CST's impact on skin barrier proteins, tight junction (TJ) integrity, inflammatory cytokines, and AD-like symptoms.

Results

CST administration led to a significant upregulation of skin barrier proteins and improved TJ function, counteracting the negative effects of Th2 cytokines on these parameters. In a 2,4-dinitrochlorobenzene-induced AD mouse model, CST treatment markedly reduced AD-like symptoms, including ear thickness, transepidermal water loss, and scratching behavior, and normalized barrier protein expression and TJ barrier function. Furthermore, CST was found to interact with the Notch1 receptor, activating the Notch1/PKC pathway, which may underlie its skin barrier-enhancing properties.

Conclusions

Collectively, these findings suggest CST as a promising therapeutic agent for AD, capable of enhancing skin barrier function, modulating immune responses, and targeting the Notch1/PKC pathway, offering a novel approach to AD treatment focusing on barrier restoration and immune modulation.
背景:特应性皮炎(AD)是一种常见的慢性炎症性皮肤病,其特征是皮肤屏障受损和免疫反应增强。该研究调查了catestatin (CST)的治疗效果,catestatin是一种铬粒蛋白a衍生的抗菌肽,可缓解ad样症状。方法:利用角化细胞培养和C57BL/6小鼠模型,研究了CST对皮肤屏障蛋白、紧密连接(TJ)完整性、炎症细胞因子和ad样症状的影响。结果:CST可显著上调皮肤屏障蛋白,改善TJ功能,抵消Th2细胞因子对这些参数的负面影响。在2,4-二硝基氯苯诱导的AD小鼠模型中,CST治疗显著减少AD样症状,包括耳厚、经皮失水和抓伤行为,并使屏障蛋白表达和TJ屏障功能正常化。此外,CST被发现与Notch1受体相互作用,激活Notch1/PKC通路,这可能是其皮肤屏障增强特性的基础。综上所述,这些发现表明CST是一种很有前景的AD治疗药物,能够增强皮肤屏障功能,调节免疫反应,并靶向Notch1/PKC通路,为AD治疗提供了一种新的途径,重点是屏障恢复和免疫调节。
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引用次数: 0
Integrative omics redefining allergy mechanisms and precision medicine 综合组学重新定义过敏机制和精准医学。
IF 6.7 2区 医学 Q1 ALLERGY Pub Date : 2025-10-01 DOI: 10.1016/j.alit.2025.08.007
Ayano Fukushima-Nomura , Hiroshi Kawasaki , Masayuki Amagai
Allergic diseases are characterized by heterogeneity driven by complex interactions between genetic, environmental, and immunological factors. Conventional classifications based solely on clinical phenotypes often fails to capture the underlying molecular diversity, thereby limiting therapeutic precision and patient outcomes. Integrative omics—encompassing genomics, transcriptomics, proteomics, metabolomics, and microbiomics—has emerged as a powerful approach to redefine disease mechanisms and advance precision medicine. By integrating high-dimensional molecular data with clinical phenotyping, omics approaches enable the identification of disease endotypes, biomarker discovery, and patient stratification.
This review highlights recent developments in clinical-omics integration, with a focus on atopic dermatitis (AD) as a prototypical allergic disease. Drawing from our studies, we illustrate how tissue-level transcriptomic profiling, combined with unbiased computational analysis, can uncover immunological heterogeneity and treatment-response patterns in AD. Additional examples in asthma and food allergy demonstrate how integrated multi-omics can uncover gene-environment interactions and elucidate mechanisms behind disease severity and health disparities.
We also address practical and ethical challenges in data harmonization, privacy, and interoperability, and underscore the critical role of computational methods and infrastructure development in enabling clinically meaningful interpretation. Importantly, successful translation of multi-omics data into clinical practice requires iterative, interdisciplinary collaboration between clinicians, data scientists, and basic researchers.
By bridging molecular complexity and clinical heterogeneity, integrative omics is reshaping the landscape of allergy research. As technologies evolve, this framework will be crucial for developing predictive models and personalized therapeutic strategies, ultimately bringing us closer to individualized, data-driven care in allergic diseases.
变应性疾病的特点是由遗传、环境和免疫因素之间复杂的相互作用驱动的异质性。仅基于临床表型的传统分类往往无法捕获潜在的分子多样性,从而限制了治疗精度和患者结果。整合组学——包括基因组学、转录组学、蛋白质组学、代谢组学和微生物组学——已经成为重新定义疾病机制和推进精准医学的有力方法。通过将高维分子数据与临床表型相结合,组学方法能够识别疾病内型、发现生物标志物和患者分层。本文综述了临床-组学整合的最新进展,重点关注特应性皮炎(AD)作为一种典型的过敏性疾病。根据我们的研究,我们说明了组织水平的转录组学分析,结合无偏倚的计算分析,如何揭示AD的免疫异质性和治疗反应模式。哮喘和食物过敏的其他例子表明,综合多组学可以揭示基因与环境的相互作用,并阐明疾病严重程度和健康差异背后的机制。我们还解决了数据协调、隐私和互操作性方面的实际和伦理挑战,并强调了计算方法和基础设施发展在实现临床有意义的解释方面的关键作用。重要的是,将多组学数据成功转化为临床实践需要临床医生、数据科学家和基础研究人员之间反复的跨学科合作。通过桥接分子复杂性和临床异质性,整合组学正在重塑过敏研究的景观。随着技术的发展,这一框架将对开发预测模型和个性化治疗策略至关重要,最终使我们更接近个性化、数据驱动的过敏性疾病护理。
{"title":"Integrative omics redefining allergy mechanisms and precision medicine","authors":"Ayano Fukushima-Nomura ,&nbsp;Hiroshi Kawasaki ,&nbsp;Masayuki Amagai","doi":"10.1016/j.alit.2025.08.007","DOIUrl":"10.1016/j.alit.2025.08.007","url":null,"abstract":"<div><div>Allergic diseases are characterized by heterogeneity driven by complex interactions between genetic, environmental, and immunological factors. Conventional classifications based solely on clinical phenotypes often fails to capture the underlying molecular diversity, thereby limiting therapeutic precision and patient outcomes. Integrative omics—encompassing genomics, transcriptomics, proteomics, metabolomics, and microbiomics—has emerged as a powerful approach to redefine disease mechanisms and advance precision medicine. By integrating high-dimensional molecular data with clinical phenotyping, omics approaches enable the identification of disease endotypes, biomarker discovery, and patient stratification.</div><div>This review highlights recent developments in clinical-omics integration, with a focus on atopic dermatitis (AD) as a prototypical allergic disease. Drawing from our studies, we illustrate how tissue-level transcriptomic profiling, combined with unbiased computational analysis, can uncover immunological heterogeneity and treatment-response patterns in AD. Additional examples in asthma and food allergy demonstrate how integrated multi-omics can uncover gene-environment interactions and elucidate mechanisms behind disease severity and health disparities.</div><div>We also address practical and ethical challenges in data harmonization, privacy, and interoperability, and underscore the critical role of computational methods and infrastructure development in enabling clinically meaningful interpretation. Importantly, successful translation of multi-omics data into clinical practice requires iterative, interdisciplinary collaboration between clinicians, data scientists, and basic researchers.</div><div>By bridging molecular complexity and clinical heterogeneity, integrative omics is reshaping the landscape of allergy research. As technologies evolve, this framework will be crucial for developing predictive models and personalized therapeutic strategies, ultimately bringing us closer to individualized, data-driven care in allergic diseases.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 514-524"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103180","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}
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Allergology International
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