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树突状细胞-CD4 T细胞相互作用:白细胞介素-4/白细胞介素-13在屋尘螨过敏患者血清免疫球蛋白E水平中的不同作用

Dendritic cell-CD4 T cell interaction: The differential role of IL-4/IL-13 in serum IgE levels in house dust mite allergic patients.

作者信息

Cernescu Luminita Daniela, Haidar Laura, Panaitescu Carmen

机构信息

Discipline of Dermatovenerology, Department XIV Microbiology, 'Victor Babes' University of Medicine and Pharmacy Timisoara, Timisoara RO-300041, Romania.

Discipline of Physiology, Department III Functional Sciences, 'Victor Babes' University of Medicine and Pharmacy Timisoara, Timisoara RO-300041, Romania.

出版信息

Exp Ther Med. 2021 Jan;21(1):95. doi: 10.3892/etm.2020.9527. Epub 2020 Nov 26.

Abstract

Allergic asthma is a chronic airway inflammatory disorder triggered by inhalant allergens. Interleukin (IL)-4 and IL-13 play a main role in the generation of T helper cell type 2 (Th2) immune response, induction of immunoglobulin E (IgE) synthesis and persistence of airway inflammation. The aim of the present study was to investigate the influence of allergen Der p 1, the major allergen of house dust mite, on the synthesis of IL-4 and IL-13 by monocyte-derived dendritic cells (DCs) and naive CD4 T cells cocultured with DCs, as well as their role in the production of serum IgE, in house dust mite (HDM) allergic patients. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients allergic to HDM and healthy donors and incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 to generate immature DCs. The obtained cells were stimulated for 24 h with Der p 1 to induce DC maturation, washed, and afterwards cocultured for 24 h with autologous naive CD4 T cells. Culture supernatants were harvested for IL-4, IL-13 and IFN-γ level measurements. DCs stimulation with Der p 1 induced higher synthesis of IL-4 and IL-13 in HDM allergic patients, compared to healthy donors. The allergic group showed significant correlation between IL-13 production by Der p 1-pulsed DCs, and total serum IgE and IL-4 production of the same cells and Der p-specific IgE. To conclude, IL-4 and IL-13 are critically related to the regulation of serum IgE production in patients with allergic asthma. The relevance of these two cytokines in the pathophysiology of Th2 asthma endotype makes them an appropriate target in its management.

摘要

过敏性哮喘是一种由吸入性过敏原引发的慢性气道炎症性疾病。白细胞介素(IL)-4和IL-13在2型辅助性T细胞(Th2)免疫反应的产生、免疫球蛋白E(IgE)合成的诱导以及气道炎症的持续存在中起主要作用。本研究的目的是调查屋尘螨主要过敏原变应原Der p 1对单核细胞来源的树突状细胞(DCs)以及与DCs共培养的初始CD4 T细胞合成IL-4和IL-13的影响,以及它们在屋尘螨(HDM)过敏患者血清IgE产生中的作用。从对HDM过敏的患者和健康供体的静脉血中分离外周血单核细胞(PBMCs),并与粒细胞-巨噬细胞集落刺激因子(GM-CSF)和IL-4一起孵育以生成未成熟DCs。用Der p 1刺激获得的细胞24小时以诱导DC成熟,洗涤后,再与自体初始CD4 T细胞共培养24小时。收集培养上清液用于测量IL-4、IL-13和IFN-γ水平。与健康供体相比,用Der p 1刺激DCs可诱导HDM过敏患者中IL-4和IL-13的更高合成。过敏组中,Der p 1刺激的DCs产生的IL-13与总血清IgE以及相同细胞产生的IL-4和Der p特异性IgE之间存在显著相关性。总之,IL-4和IL-13与过敏性哮喘患者血清IgE产生的调节密切相关。这两种细胞因子在Th2哮喘内型的病理生理学中的相关性使其成为哮喘治疗的合适靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ee/7725010/542e5e8148d5/etm-21-01-09527-g00.jpg

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