IL-5Rα marks nasal polyp IgG4-and IgE-expressing cells in aspirin-exacerbated respiratory disease
IL-5Rα marks nasal polyp IgG4-and IgE-expressing cells in aspirin-exacerbated respiratory disease
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DOI：
10.1016/j.jaci.2020.02.035
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发表时间：
2020-06-01
影响因子：
14.2
通讯作者：
Laidlaw, Tanya M.
中科院分区：
文献类型：
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作者：
Buchheit, Kathleen M.;Dwyer, Daniel F.;Laidlaw, Tanya M.
背景：阿司匹林加重的呼吸系统疾病(AERD)导致严重鼻息肉的原因尚不清楚。目的：我们试图确定AERD受试者鼻息肉中局部抗体表达细胞的上游驱动因素和表型特征。方法：鼻窦组织取自AERD、慢性鼻窦炎(CRS)合并鼻息肉(CRSwNP)、无鼻息肉的CRS和没有CRS的对照组。组织抗体水平通过酶联免疫吸附试验和免疫组织化学方法进行量化，并与疾病严重程度相关。采用单细胞RNA测序、流式细胞术和免疫荧光法检测抗体表达细胞，IL-5刺激检测IL-5Rα功能，RNA测序和定量PCR检测IL-5Rα功能。结果：AERD组织中IgE和IgG4水平明显高于对照组(P
Background: The cause of severe nasal polyposis in aspirin-exacerbated respiratory disease (AERD) is unknown. Elevated antibody levels have been associated with disease severity in nasal polyps, but upstream drivers of local antibody production in nasal polyps are undetermined.Objective: We sought to identify upstream drivers and phenotypic properties of local antibody-expressing cells in nasal polyps from subjects with AERD.Methods: Sinus tissue was obtained from subjects with AERD, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps, and controls without CRS. Tissue antibody levels were quantified via ELISA and immunohistochemistry and were correlated with disease severity. Antibody-expressing cells were profiled with single-cell RNA sequencing, flow cytometry, and immunofluorescence, with IL-5R alpha function determined through IL-5 stimulation and subsequent RNA sequencing and quantitative PCR.Results: Tissue IgE and IgG4 levels were elevated in AERD compared with in controls (P