Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps
Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps
复制标题
异位淋巴组织支持慢性鼻窦炎伴鼻息肉患者局部免疫球蛋白的产生
DOI：
10.1016/j.jaci.2017.10.014
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发表时间：
2018-03-01
影响因子：
14.2
通讯作者：
Liu, Zheng
中科院分区：
文献类型：
--
作者：
Song, Jia;Wang, Hai;Liu, Zheng
背景：异位淋巴组织（eLTs）对伴有鼻息肉的慢性鼻窦炎（CRSwNP）患者局部免疫球蛋白过度产生的作用尚不明确。
目的：我们试图探究CRSwNP患者中eLTs的细胞基础、形成机制及其功能。
方法：我们对鼻窦黏膜中的淋巴聚集进行分级，并对其结构进行组织学研究。通过实时聚合酶链反应（PCR）检测淋巴器官发生因子以及免疫球蛋白产生所需分子的表达，并利用免疫组织化学和免疫荧光方法分析它们的定位。通过流式细胞术分析滤泡辅助性T细胞的表型。使用Bio - Plex检测法或ImmunoCAP系统对免疫球蛋白水平进行定量。用屋尘螨第1组变应原（Der p 1）对鼻组织外植体进行体外激发，并使用半巢式PCR检测Iε - Cμ和Iε - Cγ环转录本的表达。
结果：与无鼻息肉的慢性鼻窦炎患者（5.66%）和对照组（3.70%）相比，嗜酸性粒细胞性（20.69%）和非嗜酸性粒细胞性（17.31%）CRSwNP患者中具有生发中心样结构的eLTs形成增加。eLTs的存在与淋巴器官发生和炎症趋化因子及细胞因子及其受体的表达增加有关。在伴有eLTs的患者中，免疫球蛋白产生所需分子的表达、滤泡辅助性T细胞的产生以及嗜酸性粒细胞性息肉中IgE的产生以及嗜酸性粒细胞性和非嗜酸性粒细胞性息肉中IgG和IgA的产生主要上调。在体外Der p 1激发后，仅在伴有eLTs的嗜酸性粒细胞性息肉中检测到Iε - Cμ转录本，而在无eLTs的息肉和非嗜酸性粒细胞性息肉中未检测到。
结论：eLTs可能支持局部免疫球蛋白的产生，因此对CRSwNP的发展有显著作用。
Background: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear.Objective: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP.Methods: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of I epsilon-C mu and I epsilon-C gamma circle transcripts was detected by using seminested PCR.Results: Increased formation of eLTs with germinal center-like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, I epsilon-C mu transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps.Conclusion: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.