CCR3 gene knockout in bone marrow cells ameliorates combined allergic rhinitis and asthma syndrome (CARAS) by reducing airway inflammatory cell infiltration and Th2 cytokines expression in mice model

CCR3 gene knockout in bone marrow cells ameliorates combined allergic rhinitis and asthma syndrome (CARAS) by reducing airway inflammatory cell infiltration and Th2 cytokines expression in mice model
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骨髓细胞中的 CCR3 基因敲除通过减少小鼠模型中的气道炎症细胞浸润和 Th2 细胞因子表达来改善过敏性鼻炎和哮喘联合综合征 (CARAS)

DOI:
10.1016/j.intimp.2021.108509
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发表时间:
2022-01-05
影响因子:
5.6
通讯作者:
Yong, XiaoZhuang
Yong, XiaoZhuang
中科院分区:
医学2区
文献类型:
--
作者:
Dai, MeiNa;Zhu, XinHua;Yong, XiaoZhuang

文献摘要

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本研究旨在探讨骨髓细胞CCR3基因敲除(CCR3-KO)对过敏性鼻炎哮喘联合综合征(CARAS)小鼠模型的影响。研究发现,CCR3-KO 显着减少了小鼠嗜酸性粒细胞 (EOS) 向鼻腔 (NALF) 和支气管肺泡 (BALF) 腔的迁移,并降低了鼻粘膜和肺组织中 Th2 细胞因子(如 IL-4、IL-5 和 IL-13)的水平。此外,组织学分析显示,卵清蛋白(OVA)调节的CCR3-KO小鼠鼻粘膜结构损伤程度明显小于OVA调节的野生型(WT)小鼠,炎症细胞浸润和鼻粘液分泌减少。肺组织炎症细胞浸润明显减少,肺平滑肌层增殖和细胞外基质(ECM)产生减少。症状分析表明,CCR3-KO 可以减少抓鼻子和打喷嚏等过敏性鼻炎 (AR) 信号。还发现 CCR3-KO 可以减少 OVA 引起的体重减轻。结果表明,CCR3-KO可通过减少气道炎症细胞浸润、下调Th2细胞因子的表达来减轻CARAS小鼠的过敏性炎症症状,CCR3基因可作为治疗CARAS的靶基因。
The present study aims to investigate the effects of CCR3 gene knockout in bone marrow cells (CCR3-KO) on the mouse model of combined allergic rhinitis and asthma syndrome (CARAS). It was found that CCR3-KO significantly reduced eosinophil (EOS) migration into the nasal (NALF) and bronchoalveolar (BALF) cavities of mice, and decreased Th2 cytokines (such as, IL-4, IL-5 and IL-13) levels in nasal mucosa and lung tissues. In addition, histological analysis showed that the damage degree of nasal mucosa structure in ovalbumin (OVA) modulated CCR3-KO mice was significantly less than that in OVA modulated Wild type (WT) mice, with reduced inflammatory cell infiltration and nasal mucus secretion. The infiltration of inflammatory cells in lung tissue was significantly reduced, and the proliferation of lung smooth muscle layer and extracellular matrix (ECM) production were decreased. Symptom analysis showed that CCR3-KO can reduced allergic rhinitis (AR) signals as nose scratching and sneezing. It was also found CCR3-KO reduce OVA-induced weight loss. The results showed that CCR3-KO could reduce the symptoms of allergic inflammation in CARAS mice by reducing airway inflammatory cell infiltration and down-regulating the expression of Th2 cytokines, and CCR3 gene could be used as a target gene for the treatment of CARAS.