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链接补体 C3 和鼻息肉中的 B 细胞。

Linking Complement C3 and B Cells in Nasal Polyposis.

机构信息

Department of Otorhinolaryngology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany.

Group of Medical Systems Biology, Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.

出版信息

J Immunol Res. 2020 Jul 8;2020:4832189. doi: 10.1155/2020/4832189. eCollection 2020.

Abstract

Nasal polyposis often is characterized by a persistent inflammation of the sinonasal mucosa, disease recurrence after medical or surgical intervention, and asthma comorbidity. Dysregulated complement activation may contribute to immunologic alterations and disease. To date, there is only scattered knowledge on the source and regulation of the central complement factors in the pathogenesis of nasal polyps. Here, we aim to study complement signatures, especially the C3-C3aR axis, and focus on cellular sources and targets in nasal polyps. Expression of complement factors, including C3, C5, and the anaphylatoxin receptors, was analyzed in nasal polyp tissue samples, the corresponding inferior turbinates, and healthy controls using transcriptomic methods and protein measurements. Distinct patterns of complement expression were found in nasal polyps compared to controls, characterized by an increased C3 activation and an increase in C3aR-bearing cells. In contrast, no difference was shown for epithelial-dependent C3 production. Besides low intracellular C3-expression levels for lymphocytes in general, we could identify an enlarged B lymphocyte population in nasal polyps displaying high amounts of intracellular C3. Our data suggest a prominent role for the C3-C3aR-axis in nasal polyps and, for the first time, describe a B cell population containing high levels of intracellular C3, suggesting a new role of B cells in the maintenance of the inflammation by complement.

摘要

鼻息肉常表现为鼻黏膜的持续炎症、医学或手术干预后的疾病复发以及哮喘合并症。补体激活失调可能导致免疫改变和疾病。迄今为止,关于鼻息肉发病机制中中央补体因子的来源和调节,只有零散的知识。在这里,我们旨在研究补体特征,特别是 C3-C3aR 轴,并关注鼻息肉中的细胞来源和靶点。使用转录组学方法和蛋白质测量,分析了鼻息肉组织样本、相应的下鼻甲和健康对照中补体因子的表达,包括 C3、C5 和过敏毒素受体。与对照组相比,鼻息肉中发现了不同的补体表达模式,其特征是 C3 激活增加和 C3aR 携带细胞增加。相比之下,上皮细胞依赖性 C3 产生没有差异。除了淋巴细胞的细胞内 C3 表达水平普遍较低外,我们还可以在鼻息肉中识别出一个扩大的 B 淋巴细胞群,其细胞内 C3 含量高。我们的数据表明 C3-C3aR 轴在鼻息肉中具有重要作用,并且首次描述了含有高水平细胞内 C3 的 B 细胞群,这表明 B 细胞在通过补体维持炎症方面具有新的作用。

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