通过诱导过度表达RORα,减少了介质素-33的表达,并通过诱导过敏性鼻炎的自细胞来预防杆细胞脱粒和炎症
Wangbo Yu1,2, Jingwei Du3, Lijuan Peng4
1Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Immunity, inflammation and disease
|October 31, 2023
概括
与视网酸受体相关的孤儿受体α (RORα) 在过敏性鼻炎 (AR) 中起着至关重要的作用. RORα 抑制了NLRP3炎症酶和巨细胞脱粒化,通过自减少炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 核受体,如与视网膜酸受体相关的孤儿受体α (RORα),调节关键细胞过程,包括增殖,分化和免疫调节.
- 过敏性鼻炎 (AR) 是一种普遍的炎症状况,影响上呼吸道.
研究的目的:
- 调查RORα在过敏性鼻炎病变发生过程中的作用和潜在机制.
- 探索RORα对AR炎症途径和细胞反应的影响.
主要方法:
- 通过使用使用Derp1.1治疗的人类鼻上皮细胞 (HNEpC) 建立了体外AR细胞模型.
- 在HNEpCs中操纵了RORα (过度表达或沉默),随后与LAD2巨细胞共同培养.
- 使用卵蛋白 (OVA) 敏感化和RORα腺病毒输送,开发了体内AR小鼠模型.
- 组织病理学,免疫组织化学,西部斑,免疫光学,ELISA和Transwell测试被用于分析分子和细胞变化.
主要成果:
- 在AR患者的鼻腔粘膜中发现RORα表达被降低了.
- 暴露于derp1降低了RORα水平,同时增加了IL-33,NLRP3炎症酶激活和HNEpC迁移.
- 在Derp1治疗的HNEpC中,RORα过度表达显著降低了IL-33水平,NLRP3炎症酶活性和细胞迁移.
- 在细胞培养和AR小鼠模型中,RORα促进了自,这反过来又抑制了巨细胞降粒和NLRP3诱导的炎症.
结论:
- 在HNEpCs中,RORα作为NLRP3炎症酶的抑制剂.
- 通过增强自,RORα通过增强自来减轻AR中的质细胞脱粒和炎症.
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