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.

中文翻译：

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鼻息肉中补体C3和B细胞的连接

鼻息肉病的特征通常是鼻窦粘膜持续发炎，药物或手术干预后疾病复发以及哮喘合并症。补体激活失调可能导致免疫学改变和疾病。迄今为止，关于鼻息肉发病机理中中央补体因子的来源和调控的知识还很少。在这里，我们旨在研究补体特征，特别是C3-C3aR轴，并关注鼻息肉的细胞来源和靶标。使用转录组学方法和蛋白质测量方法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，在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，C3aR携带细胞增加。相反，上皮依赖性C3的产生没有差异。除了通常淋巴细胞的细胞内C3表达水平较低外，我们还可以在鼻息肉中发现大量B细胞，显示出大量的细胞内C3。我们的数据表明C3-C3aR轴在鼻息肉中起着重要作用，并且首次描述了含有高水平细胞内C3的B细胞群，表明B细胞在补体维持炎症中的新作用。上皮依赖性C3的产生没有差异。除了通常淋巴细胞的细胞内C3表达水平较低外，我们还可以在鼻息肉中发现大量B细胞，显示出大量的细胞内C3。我们的数据表明C3-C3aR轴在鼻息肉中起着重要作用，并且首次描述了含有高水平细胞内C3的B细胞群，表明B细胞在补体维持炎症中的新作用。上皮依赖性C3的产生没有差异。除了通常淋巴细胞的细胞内C3表达水平较低外，我们还可以在鼻息肉中发现大量的B细胞，显示出大量的细胞内C3。我们的数据表明C3-C3aR轴在鼻息肉中起着重要作用，并且首次描述了含有高水平细胞内C3的B细胞群，表明B细胞在补体维持炎症中的新作用。