Department of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, China.
Shanxi Key Laboratory of Rapid Diagnosis and Precision Treatment of Airway Allergic Diseases, Taiyuan, China.
Inflamm Res. 2024 Nov;73(11):1919-1930. doi: 10.1007/s00011-024-01940-2. Epub 2024 Sep 5.
Dysfunctional immune regulation plays a crucial role in the pathogenesis of airway allergies. Macrophages are one of the components of the immune regulation cells. The aim of this study is to elucidate the role of lysine demethylase 5 A (KDM5A) in maintaining macrophages' immune regulatory ability.
DNA was extracted from Lactobacillus rhamnosus GG to be designated as LgDNA. LgDNA was administered to the mice through nasal instillations. M2 macrophages (M2 cells) were isolated from the airway tissues using flow cytometry.
We found that airway M2 cells of mice with airway Th2 polarization had reduced amounts of IL-10 and KDM5A. Mice with Kdm5a deficiency in M2 cells showed the airway Th2 polarization. The expression of Kdm5a in airway M2 cells was enhanced by nasal instillations containing LgDNA. KDM5A mediated the effects of LgDNA on inducing the Il10 expression in airway M2 cells. Administration of LgDNA mitigated experimental airway allergy.
M2 macrophages in the airway tissues of mice with airway allergy show low levels of KDM5A. By upregulating KDM5A expression, LgDNA can increase Il10 expression and reconcile airway Th2 polarization.
功能失调的免疫调节在气道过敏的发病机制中起着关键作用。巨噬细胞是免疫调节细胞的组成部分之一。本研究旨在阐明赖氨酸去甲基酶 5A(KDM5A)在维持巨噬细胞免疫调节能力中的作用。
从鼠李糖乳杆菌 GG 中提取 DNA,命名为 LgDNA。通过鼻腔滴注将 LgDNA 给予小鼠。使用流式细胞术从气道组织中分离 M2 巨噬细胞(M2 细胞)。
我们发现,气道 Th2 极化的小鼠气道 M2 细胞中 IL-10 和 KDM5A 的含量减少。M2 细胞中 Kdm5a 缺陷的小鼠表现出气道 Th2 极化。鼻内滴注含有 LgDNA 可增强气道 M2 细胞中 Kdm5a 的表达。KDM5A 介导了 LgDNA 对诱导气道 M2 细胞中 Il10 表达的影响。给予 LgDNA 可减轻实验性气道过敏。
气道过敏小鼠气道组织中的 M2 巨噬细胞显示低水平的 KDM5A。通过上调 KDM5A 表达,LgDNA 可以增加 Il10 表达并调和气道 Th2 极化。