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CB2R-cAMP-Epac1 pathway orchestrates epithelial-neural-immune interactions in atopic dermatitis

文献类型：期刊论文

作者Hu, Ximin2,3,4; Luo, Yi2; Zhang, Yiya1,4,5; Liu, Kun6; Wu, Liyan2; Hou, Jinjun2,8; Zhao, Guodun2; Wang, Ting2; Liu, Yifei2; Cheng, Hongyi6
刊名JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
出版日期2025-12-01
卷号156期号:6页码:14
关键词Atopic dermatitis keratinocyte CB2R Epac1 chronicitch
ISSN号0091-6749
DOI10.1016/j.jaci.2025.08.021
通讯作者Xu, Heng(xuh1990@gmail.com) ; Feng, Jing(fengjing@simm.ac.cn)
英文摘要Background: Keratinocytes form the skin's first line of defense, not only serving as a physical barrier but also actively communicating with immune cells and sensory neurons. Objective: This study elucidated the molecular mechanisms by which keratinocytes contribute to barrier dysfunction and neuroimmune activation in atopic dermatitis (AD). Methods: Cannabinoid receptor 2 (CB2R) expression was assessed by RNA sequencing, quantitative reverse transcription PCR (qRT-PCR), RNAscope fluorescence, and Western blot analysis. Pharmacologic activation/inhibition or keratinocytespecific deletion of CB2R was used to determine its role in AD-associated itch and inflammation. Behavioral assays, immunofluorescence, and qRT-PCR were used to identify downstream signaling components. Results: CB2R expression was upregulated in the epidermis of MC903-induced AD. CB2R activation alleviated scratching and skin pathology, whereas keratinocyte-specific CB2R deletion exacerbated both. CB2R suppressed adenylate cyclase 3 activity, reducing cAMP levels and downstream Epac1 activation, thereby limiting IL-33 production. This CB2R-cAMP-Epac1-IL-33 axis regulated epidermal hyperplasia, dermal neutrophil infiltration, and chronic itch. Conclusion: The keratinocyte CB2R-cAMP-Epac1 axis integrates epithelial, neural, and immune signaling to drive AD pathology, representing a potential therapeutic target for chronic itch and skin inflammation.
WOS关键词SENSORY NEURONS ; ENDOCANNABINOID SYSTEM ; CANNABINOID RECEPTOR ; CB2 ; ACTIVATION ; BACTERIAL ; PROTEINS ; CELLS ; AXIS
WOS研究方向Allergy ; Immunology
语种英语
WOS记录号WOS:001636881900001
出版者MOSBY-ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/322399]  
专题中国科学院上海药物研究所
通讯作者Xu, Heng; Feng, Jing
作者单位1.Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China
2.Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai, Peoples R China
3.South China Univ Technol, Guangzhou Peoples Hosp 1, Dept Burn & Plast Surg, Guangzhou, Peoples R China
4.Cent South Univ, Dept Dermatol, Changsha, Peoples R China
5.Cent South Univ, Hunan Key Lab Aging Biol, Changsha, Peoples R China
6.China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing, Peoples R China
7.Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Engn Res Ctr TCM Standardizat Technol, Shanghai, Peoples R China
9.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Hu, Ximin,Luo, Yi,Zhang, Yiya,et al. CB2R-cAMP-Epac1 pathway orchestrates epithelial-neural-immune interactions in atopic dermatitis[J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,2025,156(6):14.
APA Hu, Ximin.,Luo, Yi.,Zhang, Yiya.,Liu, Kun.,Wu, Liyan.,...&Feng, Jing.(2025).CB2R-cAMP-Epac1 pathway orchestrates epithelial-neural-immune interactions in atopic dermatitis.JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,156(6),14.
MLA Hu, Ximin,et al."CB2R-cAMP-Epac1 pathway orchestrates epithelial-neural-immune interactions in atopic dermatitis".JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 156.6(2025):14.

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来源：上海药物研究所

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