嗜酸性粒细胞中 CD69 信号分别通过 Erk1/2 和 JNK 通路诱导 IL-10 产生和细胞凋亡。

CD69 Signaling in Eosinophils Induces IL-10 Production and Apoptosis via the Erk1/2 and JNK Pathways, Respectively.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Osaka 573-1010, Japan.

Allergy and Clinical Immunology Department, Hanoi Medical University, Hanoi 115000, Vietnam.

出版信息

Biomolecules. 2024 Mar 18;14(3):360. doi: 10.3390/biom14030360.

DOI:10.3390/biom14030360

PMID:38540778

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10968075/

Abstract

INTRODUCTION

Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of infiltrated eosinophils. However, biological CD69 signaling activity in eosinophils remains unclear.

METHODS

CD69 expression on lung tissue eosinophils obtained from mice with ovalbumin-induced asthma was measured using flow cytometry. CD69 crosslinking was performed on eosinophils purified from the spleen of IL-5 transgenic mice to investigate CD69 signaling and its function in eosinophils. Then, qPCR, Western blot, enzyme-linked immunosorbent assay, and survival assay results were analyzed.

RESULTS

Surface CD69 expression on lung tissue eosinophils in the asthma mice model was 2.91% ± 0.76%, whereas no expression was detected in the healthy group. CD69-expressed eosinophils intrinsically have an upregulation of IL-10 mRNA expression. Moreover, CD69 crosslinking induced further pronounced IL-10 production and apoptosis; these responses were mediated via the Erk1/2 and JNK pathways, respectively.

CONCLUSIONS

Our results suggested that CD69 eosinophils play an immunoregulator role in type 2 inflammation, whereas activated tissue eosinophils contribute to the pathogenesis of asthma.

摘要

简介

嗜酸性粒细胞参与过敏疾病的发病机制，包括哮喘、过敏性鼻炎和特应性皮炎。我们之前报道过，与血液嗜酸性粒细胞相比，人组织嗜酸性粒细胞的 CD69 表达更高，其表达与疾病严重程度和浸润嗜酸性粒细胞的数量相关。然而，嗜酸性粒细胞中 CD69 的生物学信号转导活性仍不清楚。

方法

通过流式细胞术检测卵清蛋白诱导的哮喘小鼠肺组织嗜酸性粒细胞上的 CD69 表达。对 IL-5 转基因小鼠脾中纯化的嗜酸性粒细胞进行 CD69 交联，以研究 CD69 信号转导及其在嗜酸性粒细胞中的功能。然后，分析 qPCR、Western blot、酶联免疫吸附试验和存活试验的结果。

结果

哮喘小鼠模型中肺组织嗜酸性粒细胞表面 CD69 的表达为 2.91%±0.76%，而健康组未检测到表达。表达 CD69 的嗜酸性粒细胞固有地具有较高的 IL-10 mRNA 表达。此外，CD69 交联诱导了进一步明显的 IL-10 产生和细胞凋亡；这些反应分别通过 Erk1/2 和 JNK 途径介导。