Cross-talk between TH2 and TH17 pathways in patients with chronic rhinosinusitis with nasal polyps

Cross-talk between TH2 and TH17 pathways in patients with chronic rhinosinusitis with nasal polyps
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慢性鼻窦炎伴鼻息肉中 Th2 和 Th17 通路之间的串扰

DOI:
10.1016/j.jaci.2019.06.023
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发表时间:
2019-11-01
影响因子:
14.2
通讯作者:
Bachert, Claus
Bachert, Claus
中科院分区:
医学1区
文献类型:
--
作者:
Wang, Min;Zhang, Nan;Bachert, Claus

文献摘要

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背景:慢性鼻窦炎伴鼻息肉(CRSwNP)是一种具有多种内源性类型的异质性疾病。T(H)2-和T(H)17相关细胞因子是参与CRSwNP相关炎症的两种中枢调节因子。目的:研究中国CRSwNP患者中T(H)2和T(H)17通路的相互调节。方法:检测CRSwNP患者息肉组织匀浆中关键T(H)2-和T(H)17相关因子的水平。按组织IL-5和IL-17浓度分组,分析这些因子及其表达的关系。研究了分散鼻息肉细胞中T(H)2和T(H)17细胞因子的交叉调控及地塞米松治疗的效果。还探讨了T(H)2-和T(H)17相关因素与共病特应性状态、哮喘、疾病复发和水肿评分之间的关系。结果:根据相互排斥的T(H)2-和T(H)17相关因子的表达或不表达将四个CRSwNP组分类。T(H)2细胞因子IL-4和IL-13抑制T(H)17相关因子的表达,而T(H)17细胞因子IL-17和tgf - β 1增强T(H)2相关因子的表达。地塞米松对T(H)2和T(H)17通路均有抑制作用。患者的特应性状态与其T(H)2免疫应答有关。水肿评分与T(H)2通路呈正相关,与T(H)17通路负相关。结论:T(H)2和T(H)17通路相互排斥、相互调节,有利于中国CRSwNP患者T(H)2免疫应答的发生。
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a spectrum of endotypes. T(H)2- and T(H)17-related cytokines are 2 central regulators involved in the inflammation associated with CRSwNP.Objective: We sought to investigate the interregulation of T(H)2 and T(H)17 pathways in Chinese patients with CRSwNP. Methods: Levels of key T(H)2- and T(H)17-related factors were measured in homogenates of polyp tissue obtained from patients with CRSwNP. The relationship of these factors and their expression in groups classified according to tissue IL-5 and IL-17 concentrations were analyzed. Cross-regulation of T(H)2 and T(H)17 cytokines and the effects of dexamethasone treatment were studied in dispersed nasal polyp cells. Associations between T(H)2- and T(H)17 related factors and comorbid atopic status and asthma, disease recurrence, and edema scores were also explored.Results: Four CRSwNP groups were classified based on expression or nonexpression of mutually exclusive T(H)2- and T(H)17-related factors. The T(H)2 cytokines IL-4 and IL-13 inhibited expression of T(H)17-related factors, whereas the T(H)17 cytokines IL-17 and TGF-beta 1 enhanced expression of T(H)2-related factors. Dexamethasone treatment inhibited both the T(H)2 and T(H)17 pathways. A patient's atopic status was related to their T(H)2 immune response. Edema scores were positively correlated with the T(H)2 pathway and negatively correlated with the T(H)17 pathway.Conclusion: The T(H)2 and T(H)17 pathways are mutually exclusive and regulate each other, favoring the development of a T(H)2 immune response in Chinese patients with CRSwNP.