A genetic variant near <i>TSLP</i> is associated with chronic rhinosinusitis with nasal polyps and aspirin-exacerbated respiratory disease in Japanese populations
A genetic variant near <i>TSLP</i> is associated with chronic rhinosinusitis with nasal polyps and aspirin-exacerbated respiratory disease in Japanese populations
复制标题
<i>TSLP</i> 附近的基因变异与日本人群中慢性鼻窦炎伴鼻息肉和阿司匹林加剧的呼吸道疾病有关
DOI：
10.1016/j.alit.2019.06.007
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发表时间：
2020
影响因子：
6.8
通讯作者：
Tamari M
中科院分区：
文献类型：
--
作者：
Nakayama T;Hirota T;Asaka D;Sakashita M;Ninomiya T;Morikawa T;Okano M;Haruna S;Yoshida N;Takeno S;Tanaka Y;Yoshikawa M;Ishitoya J;Hizawa N;Isogai S;Mitsui C;Taniguchi M;Kojima H;Fujieda S;Tamari M
慢性鼻窦炎伴鼻息肉（CRSwNP）是一种与哮喘相关的异质性疾病，疾病严重程度高，生活质量差。一些CRSwNP患者有一种特殊的疾病，称为阿司匹林加重呼吸系统疾病（AERD），其特征是三种症状，包括CRSwNP、哮喘和对非甾体抗炎药（NSAIDs）的敏感性。1,2全基因组关联研究（GWASs）发现胸腺基质淋巴生成素（TSLP）位点与哮喘、过敏性鼻炎、嗜酸性食管炎和鼻息肉之间存在显著关联（补充表1）。3 TSLP由屏障上皮细胞产生，在激活2型相关炎症细胞（包括TH2淋巴细胞、2型先天淋巴样细胞、嗜酸性粒细胞、嗜碱性粒细胞和肥大细胞）中起核心作用。最近的一项研究检测了CRSwNP和AERD患者鼻息肉中TSLP、IL-25和IL-33的存在，发现与对照组相比，CRSwNP和AERD患者鼻息肉中TSLP mRNA显著升高。5另一项研究表明，TSLP激活嗜酸性粒细胞，并通过肥大细胞诱导肥大细胞源性PGD2的表达，在AERD的病理生理中起关键作用。为了提高我们对CRSwNP和AERD的分子机制的理解，我们进行了CRSwNP和AERD与TSLP位点遗传变异的关联研究（补充表2）。
Chronic rhinosinusitis with nasal polyps (CRSwNP), is a heterogenous disease associated with asthma, high degrees of disease severity, and a poor quality of life. 1 Some patients with CRSwNP have a specific condition called aspirin-exacerbated respiratory disease (AERD) which is characterized by a triad of symptoms including CRSwNP, asthma, and sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). 1, 2Genome-wide association studies (GWASs) have found significant associations between the thymic stromal lymphopoietin (TSLP) locus and asthma, allergic rhinitis, eosinophilic esophagitis, and nasal polyps (Supplementary Table 1). 3 TSLP is produced by barrier epithelial cells and plays a central role in activating type 2-related inflammatory cells including TH2 lymphocytes, type 2 innate lymphoid cells, eosinophils, basophils, and mast cells. 2, 4 A recent study examined the presence of TSLP, IL-25 and IL-33 in nasal polyps from patients with CRSwNP and AERD and found significant elevations of TSLP mRNA in nasal polyps from CRSwNP and AERD compared to controls. 5 Another study has shown that TSLP activates eosinophils and induces the expression of mast cell-derived PGD2 via mast cells, which plays a crucial role in the pathophysiology of AERD. 2 To improve our understanding of the molecular mechanisms of the CRSwNP and AERD, we performed an association study of CRSwNP and AERD with genetic variants in the TSLP locus (Supplementary Table 2).