Bing Yan1, Hongfei Lou2, Yang Wang1, Ying Li1, Yifan Meng2, Sihan Qi1, Ming Wang1, Lei Xiao3, Chengshuo Wang4, Luo Zhang5. 1. Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China. 2. Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China. 3. Department of Medicine, University of Illinois at Chicago, Chicago, Ill. 4. Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China. Electronic address: wangcs830@126.com. 5. Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China; Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China. Electronic address: dr.luozhang@139.com.
Abstract
BACKGROUND: The interaction between epithelial cells and immune cells plays an important role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP); however, the mechanism or mechanisms underlying TH-biased inflammation in this process are largely unknown. Profiling protein expression in patients with CRSwNP by using shotgun proteomics suggested that cystatin SN (CST1), a type 2 cysteine protease inhibitor, might play a role because this was expressed with the greatest difference in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and those with noneosinophilic chronic rhinosinusitis with nasal polyps (nonECRSwNP). OBJECTIVES: We sought to investigate the expression and role of CST1 in modulating eosinophilic inflammation in patients with CRSwNP. METHODS: Sinonasal tissues were collected from 192 patients with ECRSwNP, 52 patients with nonECRSwNP, and 40 control subjects. CST1 mRNA expression, localization, and concentration in the tissues were measured by using real-time PCR, in situ hybridization, immunohistochemistry, and an ELISA. Recombinant CST1 was used to further explore the function of the molecule in dispersed nasal polyp cells and eosinophils extracted from polyp tissues and peripheral blood. RESULTS: CST1 was mainly expressed by epithelial cells and significantly increased in patients with ECRSwNP but decreased in patients with nonECRSwNP compared with that in control subjects. CST1 expression was further increased in patients with ECRSwNP and comorbid asthma and correlated with eosinophil percentages in tissue samples. CST1 was induced by IL-4 and IL-13 in tissue from both patients with ECRSwNP and those with nonECRSwNP and repressed by IL-17A in patients with nonECRSwNP in the presence of neutrophils. CST1 enhanced eosinophil activation and recruitment through induction of IL-5. CONCLUSION: Epithelium-derived CST1 modulates eosinophil activation and recruitment, expression of which could be regulated by TH2 and TH17 cytokines.
BACKGROUND: The interaction between epithelial cells and immune cells plays an important role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP); however, the mechanism or mechanisms underlying TH-biased inflammation in this process are largely unknown. Profiling protein expression in patients with CRSwNP by using shotgun proteomics suggested that cystatin SN (CST1), a type 2 cysteine protease inhibitor, might play a role because this was expressed with the greatest difference in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and those with noneosinophilic chronic rhinosinusitis with nasal polyps (nonECRSwNP). OBJECTIVES: We sought to investigate the expression and role of CST1 in modulating eosinophilic inflammation in patients with CRSwNP. METHODS: Sinonasal tissues were collected from 192 patients with ECRSwNP, 52 patients with nonECRSwNP, and 40 control subjects. CST1 mRNA expression, localization, and concentration in the tissues were measured by using real-time PCR, in situ hybridization, immunohistochemistry, and an ELISA. Recombinant CST1 was used to further explore the function of the molecule in dispersed nasal polyp cells and eosinophils extracted from polyp tissues and peripheral blood. RESULTS:CST1 was mainly expressed by epithelial cells and significantly increased in patients with ECRSwNP but decreased in patients with nonECRSwNP compared with that in control subjects. CST1 expression was further increased in patients with ECRSwNP and comorbid asthma and correlated with eosinophil percentages in tissue samples. CST1 was induced by IL-4 and IL-13 in tissue from both patients with ECRSwNP and those with nonECRSwNP and repressed by IL-17A in patients with nonECRSwNP in the presence of neutrophils. CST1 enhanced eosinophil activation and recruitment through induction of IL-5. CONCLUSION: Epithelium-derived CST1 modulates eosinophil activation and recruitment, expression of which could be regulated by TH2 and TH17 cytokines.
Authors: Angela L Nocera; Sarina K Mueller; Alan D Workman; Dawei Wu; Kristen McDonnell; Peter M Sadow; Mansoor M Amiji; Benjamin S Bleier Journal: J Allergy Clin Immunol Date: 2022-05-31 Impact factor: 14.290
Authors: Ulrika Käck; Elisabet Einarsdottir; Marianne van Hage; Anna Asarnoj; Anna James; Anna Nopp; Kaarel Krjutškov; Shintaro Katayama; Juha Kere; Gunnar Lilja; Cilla Söderhäll; Jon R Konradsen Journal: ERJ Open Res Date: 2021-04-19
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