Circadian rhythm disruption exacerbates Th2-like immune response in murine allergic airway inflammation.

Circadian rhythm disruption exacerbates Th2-like immune response in murine allergic airway inflammation.
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昼夜节律紊乱加剧小鼠过敏性气道炎症中的 Th2 样免疫反应

DOI:
10.1002/alr.22914
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发表时间:
2022-05
影响因子:
6.4
通讯作者:
Zhao, Chang-Qing
Zhao, Chang-Qing
中科院分区:
医学1区
文献类型:
--
作者:
Cheng, Feng-Li;An, Yun-Fang;Xue, Jin-Mei;Wang, Yan-Jie;Ding, Xue-Wei;Zhang, Yan-Ting;Zhao, Chang-Qing

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慢性时差(CJL)诱导的昼夜节律紊乱(CRD)与过敏性疾病的风险增加呈正相关。然而,关于变应性鼻炎(AR)的发病机制知之甚少。将异常光/暗周期诱导的CRD小鼠随机分为阴性对照(NC)组、AR组、CRD+NC组和CRD+AR组(n = 8/组)。卵清蛋白(OVA)激发后,记录鼻症状评分。采用逆转录-定量聚合酶链反应(RT-PCR)和免疫组化染色检测鼻黏膜和肺组织中Occludin和ZO-1的表达。采用酶联免疫吸附试验(ELISA)测定血浆中OVA特异性免疫球蛋白E(sIgE)和辅助性T细胞(Th)相关细胞因子水平,采用流式细胞术评价脾细胞中Th 1、Th 2、Th 17和调节性T细胞(Treg)比例。在嗜酸性粒细胞浸润、肥大细胞脱粒和杯状细胞增生方面,CRD+AR组的鼻部症状评分显著高于AR组。CRD+AR组鼻黏膜和肺组织中ZO-1和Occludin的表达均显著低于AR组。此外,与AR组相比,CRD+AR组中脾细胞的Th 2和Th 17细胞计数以及血浆中的OVA-sIgE、白细胞介素4(IL-4)、IL-6、IL-13和IL-17 A水平显著升高,而CRD + AR组中Th 1和Treg细胞计数以及干扰素γ(IFN-γ)水平显著降低。CRD在实验上模拟了人类活动中的CJL,可能加剧AR小鼠的局部和全身过敏反应,部分原因是降低呼吸道粘膜中的Occludin和ZO-1水平,增加脾细胞中的Th 2样免疫应答。
Chronic jet lag (CJL)‐induced circadian rhythm disruption (CRD) is positively correlated with an increased risk of allergic diseases. However, little is known about the mechanism involved in allergic rhinitis (AR). Aberrant light/dark cycles‐induced CRD mice were randomly divided into negative control (NC) group, AR group, CRD+NC group, and CRD+AR group (n = 8/group). After ovalbumin (OVA) challenge, nasal symptom scores were recorded. The expression of Occludin and ZO‐1 in both nasal mucosa and lung tissues was detected by reverse transcription–quantitative polymerase chain reaction (RT‐PCR) and immunohistochemical staining. The level of OVA–specific immunoglobulin E (sIgE) and T‐helper (Th)‐related cytokines in the plasma was measured by enzyme‐linked immunosorbent assay (ELISA), and the proportion of Th1, Th2, Th17, and regulatory T cell (Treg) in splenocytes was evaluated by flow cytometry. The nasal symptom score in the CRD+AR group was significantly higher than those in the AR group with respect to eosinophil infiltration, mast cell degranulation, and goblet cell hyperplasia. The expression of ZO‐1 and Occludin in the nasal mucosa and lung tissues in the CRD+AR group were significantly lower than those in the AR group. Furthermore, Th2 and Th17 cell counts from splenocytes and OVA‐sIgE, interleukin 4 (IL‐4), IL‐6, IL‐13, and IL‐17A levels in plasma were significantly increased in the CRD+AR group than in the AR group, whereas Th1 and Treg cell count and interferon γ (IFN‐γ) level were significantly decreased in the CRD+AR group. CRD experimentally mimicked CJL in human activities, could exacerbate local and systemic allergic reactions in AR mice, partially through decreasing Occludin and ZO‐1 level in the respiratory mucosa and increasing Th2‐like immune response in splenocytes.
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