单位：[1]Department of Otolaryngology-Head and Neck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,P.R. China华中科技大学同济医学院附属同济医院耳鼻咽喉-头颈外科[2]Institute of Allergy and Clinical Immunology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,P.R. China过敏反应科华中科技大学同济医学院附属同济医院[3]Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China[4]Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA[5]Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA[6]Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Background: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation and function of VD3 in CRSwNP. Methods: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR) and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzyme that converts 25VD3 to the active 1,25-hydroxyvitamin D3 (1,25VD3), and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence, and flow cytometry. RNA sequencing was performed to identify genes regulated by 1,25VD3 in HNECs. HNECs and polyp tissue explants were treated with 1,25VD3, 25VD3, and dexamethasone. Results: 25VD3 levels in serum and nasal tissue lysates were decreased in patients with eosinophilic and noneosinophilic CRSwNP than control subjects. The expression of VDR and CYP27B1 were reduced in eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells. VDR and CYP27B1 expression in HNECs were downregulated by interferon gamma and poly (I:C). Polyp -derived epithelial cells demonstrated an impaired ability to convert 25VD3 to 1,25VD3 than control tissues. 1,25VD3 and 25VD3 suppressed IL -36y production in HNECs and polyp tissues, and the effect of 25VD3 was abolished by siCYP27B1 treatment. Tissue 25VD3 levels negatively correlated with IL -36y expression and neutrophilic inflammation in CRSwNP. Conclusion: Reduced systemic 25VD3 level, local 1,25VD3 generation and VDR expression result in impaired VD3 signaling activation in nasal epithelial cells, thereby exaggerating IL -36y production and neutrophilic inflammation in CRSwNP.
基金：
National Key Research and Development Program of China [2022YFE0131200]; National Natural Science Foundation of China (NSFC) [81920108011, 82130030, 82000965, 81900925]
第一作者单位：[1]Department of Otolaryngology-Head and Neck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,P.R. China[2]Institute of Allergy and Clinical Immunology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,P.R. China[3]Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Otolaryngology-Head and Neck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,P.R. China[2]Institute of Allergy and Clinical Immunology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,P.R. China[3]Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China[*1]Department of Otolaryngology Head and Neck Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology No. 1095 Jiefang Avenue Wuhan 430030 China
推荐引用方式(GB/T 7714)：
Xiao Qiao,Wang Hai,Song Jia,et al.Impaired local Vitamin D3 metabolism contributes to IL-36y overproduction in epithelial cells in chronic rhinosinusitis with nasal polyps[J].RHINOLOGY.2024,62(2):doi:10.4193/Rhin23.123.
APA：
Xiao, Qiao,Wang, Hai,Song, Jia,Qin, Zeng-Yin,Pan, Li...&Liu, Zheng.(2024).Impaired local Vitamin D3 metabolism contributes to IL-36y overproduction in epithelial cells in chronic rhinosinusitis with nasal polyps.RHINOLOGY,62,(2)
MLA：
Xiao, Qiao,et al."Impaired local Vitamin D3 metabolism contributes to IL-36y overproduction in epithelial cells in chronic rhinosinusitis with nasal polyps".RHINOLOGY 62..2(2024)
