Qing Bomiao, Li Minyao, Peng Dan, Wang Junyi, Song Shuo, Mo Lihua, Li Guoping, Yang Pingchang
Laboratory of Allergy and Precision Medicine, Department of Pulmonary and Critical Care Medicine, Chengdu Institute of Respiratory Health, the Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China.
Department of General Practice Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China; Institute of Allergy & Immunology of Shenzhen University and State Key Laboratory of Respiratory Diseases Allergy Division at Shenzhen University, Shenzhen, China.
Cell Immunol. 2024 Jul-Aug;401-402:104829. doi: 10.1016/j.cellimm.2024.104829. Epub 2024 May 13.
Eosinophils account for a significant portion of immune cells in the body. It is well known that eosinophils play a role in the pathogenesis of many diseases. In which the interaction between eosinophils and other immune cells is incompletely understood. The aim of this study is to characterize the immune suppressive functions of eosinophils. In this study, an irway allergy mouse model was established. Eosinophils were isolated from the airway tissues using flow cytometry cell sorting. The RAW264.7 cell line was used to test the immune suppressive functions of eosinophils. We observed that eosinophils had immune suppressive functions manifesting inhibiting immune cell proliferation and cytokine release from other immune cells. The eosinophil's immune suppressive functions were mediated by eosinophil-derived molecules, such as eosinophil peroxidase (EPX) and major basic protein (MBP). The expression of Ras-like protein in the brain 27a (Rab27a) was detected in eosinophils, which controlled the release of MBP and EPX by eosinophils. Eosinophil mediators had two contrast effects on inducing inflammatory responses or rendering immune suppressive effects, depending on the released amounts. Administration of an inhibitor of Rab27a at proper dosage could alleviate experimental airway allergy. To sum up, eosinophils have immune suppressive functions and are also inflammation inducers. Rab27a governs the release of EPX and MBP from eosinophils, which leads to immune suppression or inflammation. Modulation of Rab27a can alleviate airway allergy responses by modulating eosinophil's immune suppressive functions, which has the translational potential for the management of eosinophil-related diseases.
嗜酸性粒细胞在体内免疫细胞中占很大比例。众所周知,嗜酸性粒细胞在许多疾病的发病机制中发挥作用。其中嗜酸性粒细胞与其他免疫细胞之间的相互作用尚未完全了解。本研究的目的是表征嗜酸性粒细胞的免疫抑制功能。在本研究中,建立了气道过敏小鼠模型。使用流式细胞术细胞分选从气道组织中分离嗜酸性粒细胞。RAW264.7细胞系用于测试嗜酸性粒细胞的免疫抑制功能。我们观察到嗜酸性粒细胞具有免疫抑制功能,表现为抑制免疫细胞增殖和其他免疫细胞释放细胞因子。嗜酸性粒细胞的免疫抑制功能由嗜酸性粒细胞衍生的分子介导,如嗜酸性粒细胞过氧化物酶(EPX)和主要碱性蛋白(MBP)。在嗜酸性粒细胞中检测到大脑中类Ras蛋白27a(Rab27a)的表达,其控制嗜酸性粒细胞释放MBP和EPX。嗜酸性粒细胞介质根据释放量对诱导炎症反应或产生免疫抑制作用有两种相反的作用。适当剂量给予Rab27a抑制剂可减轻实验性气道过敏。综上所述,嗜酸性粒细胞具有免疫抑制功能,也是炎症诱导剂。Rab27a控制嗜酸性粒细胞释放EPX和MBP,从而导致免疫抑制或炎症。调节Rab27a可以通过调节嗜酸性粒细胞的免疫抑制功能来减轻气道过敏反应,这对嗜酸性粒细胞相关疾病的治疗具有转化潜力。