Evidence map›Paper›PMID 42269941›Full record

ArticleThe Journal of allergy and clinical immunology2026

The SPRR2A-CSTA axis drives IL-17A-induced squamous metaplasia and steroid resistance in allergic rhinitis.

Shaobing Xie, Xuan Yuan, Liyuan Liu, Maonan Wu, Wenjing Gu, Hua Zhang, Zhihai Xie, Weihong Jiang, Peisong Gao

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In one paragraph

Article in The Journal of allergy and clinical immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Shaobing XieDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md; Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China.
Xuan YuanDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md; Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China.
Liyuan LiuDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
Maonan WuDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md; Department of Pediatric Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, Hunan, China.
Wenjing GuDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md; Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
Hua ZhangDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China; Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, Hunan, China.
Zhihai XieDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China; Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, Hunan, China.
Weihong JiangDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China; Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address: jiangwh68@126.com.
Peisong GaoDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: pgao1@jhmi.edu.

Funding

Environmental Pollutants Potentiate Allergic Inflammation via Functional Axis of Aryl hydrocarbon Receptor, ROS, and CaMKII in AsthmaR01AI141642 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2019 to 2024
$2.9M
Functional role of miR-511-3p in allergic asthma and its underlying mechanismsR01AI153331 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Peisong Gao · 2021 to 2026
$2.7M
NIAID NIH HHS R01 AI141642NIAID NIH HHS R01 AI153331
6 · The paper itself

Abstract

backgroundEpithelial remodeling, particularly squamous metaplasia (SM), is a common but understudied epithelial alteration in refractory allergic rhinitis (AR). Its molecular drivers and contribution to steroid resistance remain unclear.

objectiveWe sought to define the epithelial keratinization program underlying SM in AR and determine its role in glucocorticoid resistance.

methodsNasal mucosa tissues from patients with refractory AR with or without SM were assessed by immunostaining and transcriptomic profiling. Small proline-rich protein 2A (SPRR2A)-deficient mice were used to determine the role of SPRR2A in epithelial keratinization and steroid responsiveness. Primary nasal epithelial cells were stimulated with IL-17A or cystatin A (CSTA) to evaluate SPRR2A-dependent keratinization and steroid resistance. Serum SPRR2A and CSTA levels were quantified in patients with AR stratified by steroid responsiveness.

resultsTranscriptomic analysis identified SPRR2A as a leading epithelial marker associated with SM in AR. SPRR2A-associated keratin remodeling, including upregulation of KRT6A and KRT13, represented a defining molecular signature of SM. Glucocorticoid receptor β, a key mediator of steroid resistance, was markedly increased and colocalized with KRT6A and KRT13 in SM tissues. IL-17A induced a robust SPRR2A-keratin remodeling module, generating a steroid-resistant epithelial state. Genetic deletion of Sprr2a abolished IL-17A-driven keratinization, prevented SM, and restored steroid responsiveness. Mechanistically, CSTA emerged as a SPRR2A-dependent effector that promoted squamous differentiation and epithelial GRβ induction. Csta-treated primary cultures recapitulated SM and conferred steroid resistance. Clinically, elevated serum SPRR2A and CSTA levels distinguished patients with steroid-resistant AR from those with steroid-responsive AR.

conclusionsSPRR2A promotes epithelial SM and steroid resistance through CSTA, identifying the SPRR2A-CSTA axis as a potential therapeutic target and biomarker pathway in refractory AR.

Indexed as

Allergic rhinitiscystatin Asmall proline-rich protein 2Asquamous metaplasiasteroid resistance

Identifiers

PMID42269941
PMCPMC13285722

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.