Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
Clin Exp Immunol. 2010 Nov;162(2):315-24. doi: 10.1111/j.1365-2249.2010.04243.x. Epub 2010 Sep 1.
Immunoglobulins (Igs) play important immunomodulatory effects on allergic asthma. Among these, IgG has been reported to regulate allergic inflammation in previous studies about immunotherapy and intravenous immunoglobulin therapy. In this study, to examine the immunomodulatory mechanisms of IgG and FcRs we evaluated the effects of intravenous (i.v.) rabbit IgG administration (IVIgG) on allergic airway inflammation and lung antigen-presenting cells (APCs) in a murine model of ovalbumin (OVA) sensitization and challenge. In OVA-challenged mice, IVIgG attenuated airway eosinophilia, airway hyperresponsiveness and goblet cell hyperplasia and also inhibited the local T helper type (Th) 2 cytokine levels. Additionally, IVIgG attenuated the proliferation of OVA-specific CD4(+) T cells transplanted into OVA-challenged mice. Ex vivo co-culture with OVA-specific CD4(+) cells and lung CD11c(+) APCs from mice with IVIgG revealed the attenuated transcription level of Th2 cytokines, suggesting an inhibitory effect of IVIgG on CD11c(+) APCs to induce Th2 response. Next, to analyse the effects on Fcγ receptor IIb and dendritic cells (DCs), asthmatic features in Fcγ receptor IIb-deficient mice were analysed. IVIgG failed to attenuate airway eosinophilia, airway inflammation and goblet cell hyperplasia. However, the lacking effects of IVIgG on airway eosinophilia in Fcγ receptor IIb deficiency were restored by i.v. transplantation of wild-type bone marrow-derived CD11c(+) DCs. These results demonstrate that IVIgG attenuates asthmatic features and the function of lung CD11c(+) DCs via Fcγ receptor IIb in allergic airway inflammation. Targeting Fc portions of IgG and Fcγ receptor IIb on CD11c(+) DCs in allergic asthma is a promising therapeutic strategy.
免疫球蛋白（Igs）在过敏性哮喘中发挥重要的免疫调节作用。在这些 Igs 中，已有研究报道 IgG 通过调节免疫疗法和静脉注射免疫球蛋白治疗中的过敏炎症。在这项研究中，为了研究 IgG 和 Fcγ 受体的免疫调节机制，我们评估了静脉注射（i.v.）兔 IgG 给药（IVIgG）对卵清蛋白（OVA）致敏和激发的小鼠模型中过敏性气道炎症和肺抗原呈递细胞（APC）的影响。在 OVA 激发的小鼠中，IVIgG 减轻气道嗜酸性粒细胞增多、气道高反应性和杯状细胞增生，并抑制局部辅助性 T 细胞（Th）2 细胞因子水平。此外，IVIgG 抑制了移植到 OVA 激发小鼠中的 OVA 特异性 CD4+T 细胞的增殖。与 OVA 特异性 CD4+细胞和来自接受 IVIgG 的小鼠的肺 CD11c+APC 进行体外共培养揭示了 Th2 细胞因子转录水平降低，表明 IVIgG 对 CD11c+APC 具有抑制作用，可诱导 Th2 反应。接下来，为了分析 Fcγ 受体 IIb 和树突状细胞（DC）的影响，分析了 Fcγ 受体 IIb 缺陷型小鼠的哮喘特征。IVIgG 未能减轻气道嗜酸性粒细胞增多、气道炎症和杯状细胞增生。然而，在 Fcγ 受体 IIb 缺陷型小鼠中，IVIgG 对气道嗜酸性粒细胞增多的缺乏作用通过静脉注射移植野生型骨髓衍生的 CD11c+DC 得到恢复。这些结果表明，IVIgG 通过过敏性气道炎症中的 Fcγ 受体 IIb 减轻哮喘特征和肺 CD11c+DC 的功能。针对过敏性哮喘中 CD11c+DC 上的 IgG 和 Fcγ 受体 IIb 的 Fc 部分是一种有前途的治疗策略。
