Fc gamma RIIIA Negatively Impacts Humoral Immune Responses but Not Overall Lung Inflammation in an Ovalbumin-Induced Allergic Asthma Mouse Model
Fc gamma RIIIA Negatively Impacts Humoral Immune Responses but Not Overall Lung Inflammation in an Ovalbumin-Induced Allergic Asthma Mouse Model
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Fc gamma RIIIA 对卵清蛋白诱导的过敏性哮喘小鼠模型中的体液免疫反应产生负面影响，但对整体肺部炎症没有影响
DOI：
10.1159/000487539
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发表时间：
2018
影响因子：
2.8
通讯作者：
Fang Yu
中科院分区：
文献类型：
--
作者：
Zhou Pingping;Wu Tongqian;Jin Xiaoqian;Li Jing;Yan Haijian;Zhou Ling;Huang Yali;Wang Jun;Zhou Haiyan;Zhu Xiaoping;Zou Xiang;Fang Yu
Fcγ受体(FcγR)在变态反应和哮喘等病理生理过程中起着积极和消极的免疫调节作用。与经典定义为抑制性受体的FcγRIIB相比，小鼠FcγRIIIA及其人功能同源物FcγRIIA被认为是激活受体。目的分析小鼠FcγRIIIA(人FcγRIIA)和FcγRIIB在卵白蛋白(OVA)诱导的哮喘小鼠模型中的作用，并初步评估各自的FcγR与人哮喘患者循环γ水平的相关性。方法采用野生型、FcγRIIA-/-和FcγRIIIA-/-小鼠建立哮喘模型，并对以肺组织为中心的致敏病理进行评价。分析过敏性哮喘患者外周血单个核细胞FcγRIIB、FcγRIIA和FcγRIIIA的表达水平以及血清循环γ水平。结果虽然在没有FcγRIIIA的小鼠哮喘模型中观察到以OVA特异性Ig G和Ig E水平升高为特征的体液免疫应答增强，但Fc OVARIIIA并没有记录到Fc OVARIIIA对体液免疫的整体调节，特别是在肺组织炎症指标方面。正如预期的那样，在没有FcγRIIb的情况下，观察到了以血清抗体水平衡量的增强免疫反应，以及在这个小鼠哮喘模型中各种调节途径的免疫反应。在人类哮喘患者中，人FcγRIIB的表达水平与血清γ水平呈负相关，而FcγRIIA的表达水平与血清Ig E水平呈负相关。结论我们没有发现主要证据表明小鼠Fc RIIIA在卵清蛋白诱导的小鼠哮喘模型中具有免疫抑制作用。由于哮喘是一种复杂的疾病，免疫调节反应涉及复杂的成分和途径，FcγRIIIA及其人类功能同源物FcγRIIA在哮喘中的确切作用仍有待于使用其他小鼠哮喘模型和临床研究进一步阐明。
BackgroundFcγ receptors (FcγR) play substantial immune regulatory roles both positively and negatively in pathophysiological processes including allergy and asthma. Compared with FcγRIIB which is classically defined as an inhibitory receptor, mouse FcγRIIIA and its functional human homologue FcγRIIA have been assumed to be activating receptors. However, evidence demonstrating inhibitory regulation by mouse FcγRIIIA has recently been emerging.ObjectiveTo dissect the contributory roles of mouse FcγRIIIA (human FcγRIIA) in parallel with FcγRIIB in an ovalbumin (OVA)-induced mouse model of asthma and to preliminarily assess the correlation of the respective FcγR with circulating IgE levels in human asthma patients.MethodsWild-type, FcγRIIB–/–, and FcγRIIIA–/–mice were used in an OVA-induced asthma model followed by assessment of the allergic pathology focused on the lung tissues. Expression levels of FcγRIIB, FcγRIIA, and FcγRIIIA on peripheral blood mononuclear cells (PBMC) together with the circulating IgE levels in the serum from patients with allergic asthma were analysed.ResultsAlthough enhanced humoral immune responses typically represented by augmented OVA-specific IgG and IgE levels in serum were observed in the absence of FcγRIIIA in the mouse asthma model, no overall regulation by FcγRIIIA, especially in terms of those parameters measuring lung tissue inflammation, was recorded. As expected, in the absence of FcγRIIB, augmented immune responses measured as serum antibody levels as well as those in various regulatory pathways in this mouse asthma model were observed. The expression levels of human FcγRIIB but not FcγRIIA were negatively correlated with serum levels of IgE in human asthma patients.ConclusionWe did not find major evidence demonstrating an immune inhibitory role of mouse FcγRIIIA in this OVA-induced mouse asthma model. As asthma is a complex disease and the immune regulatory responses involve sophisticated components and pathways, the exact roles of FcγRIIIA as well as its human functional homologue FcγRIIA in asthma still await further clarification using other mouse asthma models as well as clinical studies.