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Multiomics insights into retinoic acid–mediated regulation of eosinophils in severe asthma 重度哮喘患者视黄酸介导嗜酸性粒细胞调节的多组学研究
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.10.029
Jun Miyata MD, PhD , Keeya Sunata MD, PhD , Hisashi Sasaki MD , Yusuke Kawashima PhD , Yo Otsu MD , Ryuta Onozato MD , Emiko Matsuyama MD , Shinichi Okuzumi MD, PhD , Takao Mochimaru MD, PhD , Katsunori Masaki MD, PhD , Hiroki Kabata MD, PhD , Ryo Konno PhD , Masaki Ishikawa PhD , Yoshinori Hasegawa PhD , Yoshifumi Kimizuka MD, PhD , Makoto Arita PhD , Koichi Fukunaga MD, PhD

Background

Severe asthma is marked by persistent eosinophilic inflammation, but the role of all-trans retinoic acid (ATRA) in eosinophil homeostasis remains unclear.

Objective

This study examined the regulatory role of ATRA in eosinophil function in severe asthma.

Methods

Multiomics analysis (transcriptomics, proteomics, and lipidomics) was conducted on blood eosinophils from healthy participants and patients with severe asthma. The effects of ATRA on eosinophil function were further analyzed by using flow cytometry and quantitative RT-PCR.

Results

Transcriptomic profiling of eosinophils from patients with severe asthma revealed a distinct gene expression signature, with upregulation of the genes GGT5, IL2RA, CCL23, and NOD2 and downregulation of SPRY2 and HIC1. This phenotype was driven by type 2 cytokines (IL-5 and IL-4) and muramyl dipeptide but was counterregulated by ATRA. Proteomic analysis showed increased expression of P-selectin glycoprotein ligand-1 in SA-EOS, which was upregulated by type 2 cytokines and downregulated by ATRA. Lipidomic analysis identified dysregulated 15-lipoxygenase metabolism in SA-EOS, with ATRA selectively inhibiting cysteinyl leukotriene metabolism while sparing the 15-lipoxygenase pathway. Multiomics analysis of eosinophils from ATRA-treated healthy participants revealed specific downregulation of IL1RL1 and IL3RA, reducing responsiveness to IL-33 and IL-3 and distinguishing them from IL-5–induced eosinophils.

Conclusion

These findings highlight the role of ATRA in maintaining eosinophil homeostasis and counterregulating IL-5–driven activation, thus offering insights into potential therapeutic strategies for severe asthma.
重度哮喘以持续的嗜酸性粒细胞炎症为特征,但全反式维甲酸(ATRA)在嗜酸性粒细胞稳态中的作用尚不清楚。目的探讨ATRA对重度哮喘患者嗜酸性粒细胞功能的调节作用。方法采用多组学(转录组学、蛋白质组学和脂质组学)对健康受试者和重度哮喘患者的血嗜酸性粒细胞进行分析。采用流式细胞术和定量RT-PCR分析ATRA对嗜酸性粒细胞功能的影响。结果重度哮喘患者嗜酸性粒细胞的转录组学分析显示,GGT5、IL2RA、CCL23和NOD2基因表达上调,SPRY2和HIC1基因表达下调,具有明显的基因表达特征。这种表型由2型细胞因子(IL-5和IL-4)和muramyl二肽驱动,但被ATRA拮抗。蛋白质组学分析显示,SA-EOS中p -选择素糖蛋白配体1的表达增加,2型细胞因子上调p -选择素糖蛋白配体1,ATRA下调p -选择素糖蛋白配体1的表达。脂质组学分析发现SA-EOS中15-脂氧合酶代谢失调,ATRA选择性抑制半胱氨酸白三烯代谢,同时保留15-脂氧合酶途径。对atra治疗的健康参与者的嗜酸性粒细胞的多组学分析显示,IL1RL1和IL3RA特异性下调,降低了对IL-33和IL-3的反应性,并将它们与il -5诱导的嗜酸性粒细胞区分出来。结论ATRA在维持嗜酸性粒细胞稳态和抑制il -5激活中的作用,为重症哮喘的潜在治疗策略提供了新的思路。
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引用次数: 0
Evaluating Diet and Nutrition-Related Concerns in a Multidisciplinary Clinic for Pediatric Patients with Atopic Dermatitis 评估儿童特应性皮炎患者的多学科临床饮食和营养相关问题
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.025
Wendy Elverson RD LDN , Tina Ho MD , Karol Timmons RN MS CPNP , Maya Dayanim , Lynda Schneider MD FAAAAI , Jennifer Lebovidge PhD
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引用次数: 0
Meeting Announcement 会议公告
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/S0091-6749(25)02241-9
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引用次数: 0
Quantitative Systems Biology Modeling Estimates Extent of Excessive Kallikrein Generation in Hereditary Angioedema Patients 定量系统生物学模型估计遗传性血管性水肿患者钾激肽过量产生的程度
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.009
Allen Kaplan MD FAAAAI , Catherine Miller PharmD, MPH , Mrinal Shah PhD , David Maag PhD , James Butler , Jonathan Phillips
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引用次数: 0
Response Drivers in Sebetralstat Placebo-controlled Clinical Trials Sebetralstat安慰剂对照临床试验中的反应驱动因素
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.016
Jonathan Bernstein MD FAAAAI , Emel Aygören-Pürsün MD , Danny Cohn MD PhD , Henriette Farkas MD PhD DSc , William Lumry MD FAAAAI , Andrea Zanichelli MD , James Hao PhD , Michael Smith PharmD , Paul Audhya MD , Erik Hansen , Nathan Teuscher , Marc Riedl MD MS
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引用次数: 0
Minimally invasive skin tape strip proteomic analysis demonstrates significant inhibition of epidermal hyperplasia protein cluster in pediatric atopic dermatitis patients treated with dupilumab 微创皮肤胶带条带蛋白质组学分析显示,在接受dupilumab治疗的儿童特应性皮炎患者中,表皮增生蛋白簇有显著的抑制作用
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.059
Elena Goleva PhD , Evgeny Berdyshev PhD , Simion Kreimer PhD , Taras Lyubchenko , Emilie Gloaguen , Inoncent Agueusop , Peck Ong MD FAAAAI , Simon Danby , Michael Cork BSc MB PhD FRCP , Joseph Zahn MD , Annie Zhang MD , Donald Leung MD PhD FAAAAI
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引用次数: 0
Concurrent Improvement Over Time in Multiple Aspects of Quality of Life in Patients with Chronic Spontaneous Urticaria Treated with Omalizumab 慢性自发性荨麻疹患者接受Omalizumab治疗后,生活质量的多个方面随着时间的推移同步改善
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.041
Giselle Mosnaim , Sarbjit Saini MD FAAAAI , Michael Holden MD, MS , Ben Trzaskoma , Jonathan Bernstein MD FAAAAI
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引用次数: 0
Navenibart Delays Time to First Attack in Hereditary Angioedema: Results from ALPHA-STAR Navenibart延迟遗传性血管性水肿的首次发作时间:来自ALPHA-STAR的结果
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.047
Raffi Tachdjian MD MPH FAAAAI , Marc Riedl MD MS , Huamin Li MD PhD FAAAAI , Karl Sitz MD , Joshua Jacobs MD , Theodora Cohen , Claire VanEenwyk , Kusumam Joseph , Christopher Morabito , William Lumry MD FAAAAI
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引用次数: 0
Serum Total IgE Reductions With Dupilumab Treatment In Pediatric Patients With Atopic Dermatitis, Asthma Or Eosinophilic Esophagitis And Their Relationship To Clinical Improvement Dupilumab治疗儿童特应性皮炎、哮喘或嗜酸性食管炎患者血清总IgE降低及其与临床改善的关系
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.020
Lisa Beck MD FAAAAI , Jonathan Spergel MD PhD FAAAAI , Emily McGowan MD PhD FAAAAI , Leonard Bacharier MD FAAAAI , Lawrence Eichenfield MD , Nikolaos Papadopoulos MD , Changming Xia PhD , Rahin Ghassemebrahimzadeh PharmD , Sonya Cyr PhD
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引用次数: 0
Preclinical Characterization of a Potent and Half-life Extended Anti-OX40L Antibody 一种强效和半衰期延长的抗ox40l抗体的临床前特征
IF 11.2 1区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.jaci.2025.12.056
Yun Zhang , Hao Ran , Tianhong Li , Chenpeng Su , Chuan Chen , Dandan Liu , Yi Pan , Xiaoou Xu , Jiyuan Tian , Maowei Wang , Liang Tian , Jian Peng , Zhenping Zhu
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引用次数: 0
期刊
Journal of Allergy and Clinical Immunology
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