Invariant natural killer T (iNKT) cells in asthma: a novel insight into the pathogenesis of asthma and the therapeutic implication of glycolipid ligands for allergic diseases.
Invariant natural killer T (iNKT) cells in asthma: a novel insight into the pathogenesis of asthma and the therapeutic implication of glycolipid ligands for allergic diseases.
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DOI：
10.2332/allergolint.r-06-137
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发表时间：
2007-03-01
期刊：
影响因子：
--
通讯作者：
Miyake, Sachiko
中科院分区：
文献类型：
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作者：
Oki, Shinji;Miyake, Sachiko
变应性支气管哮喘是一种起源于呼吸道黏膜免疫反应失调的复杂炎症性疾病。哮喘肺的炎症状态的特征在于气道粘膜中大量嗜酸性粒细胞、淋巴细胞和肥大细胞浸润，导致气道高敏性、杯状细胞增生和粘液过度产生。炎症过程被认为是强烈的辅助性T细胞（Th）2偏向性免疫应答的结果。在过去的几年里，在理解吸入暴露于过敏原后Th 2偏向反应的发展机制以及在此过程中显著参与的CD 4 + T细胞的特征方面取得了巨大进展。最近，一种新的T细胞群体，不变的自然杀伤T（iNKT）细胞已被证明在小鼠过敏性气道炎症模型的发病机制中发挥重要作用。iNKT细胞是最有效的免疫调节剂之一，通过在活化后大量产生各种细胞因子，包括IL-4和IFN-γ，并且参与各种免疫调节，包括感染、自身免疫和肿瘤监视。iNKT细胞在支气管哮喘发展中的潜在致病作用是由于它们在给定条件下产生主要Th 2细胞因子的能力。在过去的研究中，由于iNKT细胞的检测困难，iNKT细胞在哮喘发病机制中的参与可能被低估，表明CD 4 + T细胞参与哮喘。与此同时，越来越多的证据表明，iNKT细胞由于其TCR使用的不变性，对进化保守的非多态性抗原呈递分子CD 1d的限制，以及其产生Th 1和Th 2细胞因子的出色能力，可能成为基于免疫的治疗自身免疫性疾病，肿瘤和感染的有希望的靶点。本文就iNKT细胞在哮喘中的病理生理作用作一综述。我们还将讨论使用iNKT细胞的糖脂配体治疗支气管哮喘的可能方法。
Allergic bronchial asthma is a complex inflammatory diseases originated from dysregulated immune responses in the respiratory mucosa. The inflammatory state in asthmatic lung is characterized by massive infiltration with eosinophils, lymphocytes, and mast cells in the airway mucosa leading to airway hyperseisitivity, goblet cell hyperplasia and mucus overproduction. The inflammatory process is thought to be the result of intensive T helper (Th) 2-biased immune response. Over the past several years, there has been enormous progress in understanding the mechanisms for development of Th2-biased responses after inhaled exposure to allergens and the characteristics of CD4+ T cells prominently involved in this process. Recently, a new population of T cells, invariant natural killer T (iNKT) cells has been shown to play an important role in the pathogenesis of mouse model of allergic airway inflammation. iNKT cells are one of the most potent immune modulators through a massive production of a various cytokines including IL-4 and IFN-gamma upon activation, and are involved in a variety of immunoregulations including infection, autoimmunity, and tumor surveillance. The potent pathogenic role of iNKT cells in the development of bronchial asthma is due to their ability to produce predominant Th2 cytokines in a given condition. The involvement of iNKT cells in the pathogenesis of asthma might have been underestimated in the past studies demonstrating the involvement of CD4+ T cells in asthma because of the difficulty in the detection of iNKT cells. Meanwhile, growing evidences have demonstrated that iNKT cells could be a promising target for immune-based therapies for autoimmune diseases, tumor, and infection due to the invariance of their TCR usage, the restriction to the evolutionally-conserved non-polymorphic antigen-presenting molecule CD1d, and their outstanding ability to produce both Th1- and Th2-cytokines. In this review, we will overview current understanding of the pathophysiological roles of iNKT cells in asthma. We would also discuss on possible therapeutic approaches to bronchial asthma employing glycolipid ligands for iNKT cells.