Disease-Specific T-Helper Cell Polarizing Function of Lesional Dendritic Cells in Different Types of Chronic Rhinosinusitis with Nasal Polyps
Disease-Specific T-Helper Cell Polarizing Function of Lesional Dendritic Cells in Different Types of Chronic Rhinosinusitis with Nasal Polyps
复制标题
不同类型慢性鼻窦炎伴鼻息肉病变树突状细胞的疾病特异性T辅助细胞极化功能
DOI：
10.1164/rccm.201402-0234oc
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发表时间：
2014-09-15
影响因子：
24.7
通讯作者：
Liu, Zheng
中科院分区：
文献类型：
--
作者：
Shi, Li-Li;Song, Jia;Liu, Zheng
基本原理：虽然嗜酸性和非嗜酸性慢性鼻窦炎鼻息肉（CRSwNP）表现出不同的T辅助细胞（Th）反应，其内在机制尚不清楚。目的：阐明树突状细胞（DC）的表型和Th细胞极化功能在不同类型的CRSwNP。方法：DC亚群，其表面表型，和Th细胞亚群通过免疫组化和流式细胞术进行了研究。将分选的病变DC活化或与自体幼稚CD 4（+）T细胞一起培养，并通过ELISA测定细胞因子的产生。胸腺基质淋巴细胞生成素和骨桥蛋白的表达进行检测通过逆转录聚合酶链反应.测量和主要结果：虽然升高的局部Th 1和Th 17细胞，注意到在嗜酸性和noneosinophilic CRSwNP，增加Th 2细胞只发现在嗜酸性CRSwNP。在两种类型的CRSwNP中均发现骨髓DC、浆细胞样DC及其活化亚群数量增加，但只有来自嗜酸性CRSwNP的骨髓DC和浆细胞样DC表现出OX 40配体（OX 40 L）和程序性死亡配体1（PD-L1）表达上调。两种CRSwNP来源的DCs均能产生更高水平的IL-12、IL-6和转化生长因子β，并诱导Th 1和Th 17应答;相反，当与初始CD 4（+）T细胞共培养时，只有嗜酸性CRSwNP来源的DCs诱导明显增强的Th 2应答。阻断来自嗜酸性粒细胞CRSwNP的病变DC上的OX 40 L和PD-L1抑制了DC-T细胞共培养物中的Th 2应答，但促进了Th 1应答。在嗜酸性粒细胞和非嗜酸性粒细胞CRSwNP中发现了不同的病变DC亚群，其中嗜酸性粒细胞CRSwNP中的OX 40 L/PD-L1（+）病变DC可以引发Th 2细胞，而非嗜酸性粒细胞CRSwNP中低表达OX 40 L/PD-L1的病变DC主要诱导Th 1/Th 17细胞。
Rationale: Although eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying mechanisms remain unclear.Objectives: To clarify the phenotypes and Th-cell polarizing functions of dendritic cells (DCs) in different types of CRSwNP.Methods: DC subsets, their surface phenotypes, and Th-cell subsets were studied by means of immunohistochemistry and flow cytometry. The sorted lesional DCs were activated or cultured with autologous naive CD4(+) T cells, and cytokine production was determined by ELISA. Thymic stromal lymphopoietin and osteopontin expression were detected by means of reverse-transcriptase polymerase chain reaction.Measurements and Main Results: Although elevated local Th1 and Th17 cells were noted in both eosinophilic and noneosinophilic CRSwNP, increased Th2 cells were found only in eosinophilic CRSwNP. Increased numbers of myeloid DCs, plasmacytoid DCs, and their activated subsets were found in both types of CRSwNP, but only myeloid DCs and plasmacytoid DCs from eosinophilic CRSwNP demonstrated an up-regulation of OX40 ligand (OX40L) and programmed death ligand 1(PD-L1) expression. Lesional DCs from both types of CRSwNP produced enhanced levels of IL-12, IL-6, and transforming growth factor-beta, and induced increased Th1 and Th17 responses; in contrast, only DCs from eosinophilic CRSwNP induced obviously enhanced Th2 responses, when cocultured with naive CD4(+) T cells. Blockade of OX40L and PD-L1 on lesional DCs from eosinophilic CRSwNP suppressed Th2 responses, but promoted Th1 responses in DC-T cell coculture.Conclusions: Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.