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.
{"title":"Multiomics insights into retinoic acid–mediated regulation of eosinophils in severe asthma","authors":"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","doi":"10.1016/j.jaci.2025.10.029","DOIUrl":"10.1016/j.jaci.2025.10.029","url":null,"abstract":"<div><h3>Background</h3><div>Severe asthma is marked by persistent eosinophilic inflammation, but the role of all-trans retinoic acid (ATRA) in eosinophil homeostasis remains unclear.</div></div><div><h3>Objective</h3><div>This study examined the regulatory role of ATRA in eosinophil function in severe asthma.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>Transcriptomic profiling of eosinophils from patients with severe asthma revealed a distinct gene expression signature, with upregulation of the genes <em>GGT5</em>, <em>IL2RA</em>, <em>CCL23</em>, and <em>NOD2</em> and downregulation of <em>SPRY2</em> and <em>HIC1</em>. 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 2","pages":"Pages 531-539"},"PeriodicalIF":11.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461949","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}
Pub Date : 2026-02-01DOI: 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
{"title":"Evaluating Diet and Nutrition-Related Concerns in a Multidisciplinary Clinic for Pediatric Patients with Atopic Dermatitis","authors":"Wendy Elverson RD LDN , Tina Ho MD , Karol Timmons RN MS CPNP , Maya Dayanim , Lynda Schneider MD FAAAAI , Jennifer Lebovidge PhD","doi":"10.1016/j.jaci.2025.12.025","DOIUrl":"10.1016/j.jaci.2025.12.025","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 2","pages":"Page AB7"},"PeriodicalIF":11.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146871","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}
Pub Date : 2026-02-01DOI: 10.1016/S0091-6749(25)02241-9
{"title":"Meeting Announcement","authors":"","doi":"10.1016/S0091-6749(25)02241-9","DOIUrl":"10.1016/S0091-6749(25)02241-9","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 2","pages":"Page 3A"},"PeriodicalIF":11.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147100","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}
Pub Date : 2026-02-01DOI: 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
Pub Date : 2026-02-01DOI: 10.1016/j.jaci.2025.12.041
Giselle Mosnaim , Sarbjit Saini MD FAAAAI , Michael Holden MD, MS , Ben Trzaskoma , Jonathan Bernstein MD FAAAAI
{"title":"Concurrent Improvement Over Time in Multiple Aspects of Quality of Life in Patients with Chronic Spontaneous Urticaria Treated with Omalizumab","authors":"Giselle Mosnaim , Sarbjit Saini MD FAAAAI , Michael Holden MD, MS , Ben Trzaskoma , Jonathan Bernstein MD FAAAAI","doi":"10.1016/j.jaci.2025.12.041","DOIUrl":"10.1016/j.jaci.2025.12.041","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 2","pages":"Page AB12"},"PeriodicalIF":11.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147558","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}
Pub Date : 2026-02-01DOI: 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
{"title":"Navenibart Delays Time to First Attack in Hereditary Angioedema: Results from ALPHA-STAR","authors":"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","doi":"10.1016/j.jaci.2025.12.047","DOIUrl":"10.1016/j.jaci.2025.12.047","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 2","pages":"Page AB14"},"PeriodicalIF":11.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147272","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}
Pub Date : 2026-02-01DOI: 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
{"title":"Preclinical Characterization of a Potent and Half-life Extended Anti-OX40L Antibody","authors":"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","doi":"10.1016/j.jaci.2025.12.056","DOIUrl":"10.1016/j.jaci.2025.12.056","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 2","pages":"Page AB17"},"PeriodicalIF":11.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147392","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}
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