Salazar Fabián, Ghaemmaghami Amir M
Division of Immunology, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham , UK.
Front Immunol. 2013 Nov 4;4:356. doi: 10.3389/fimmu.2013.00356.
Allergy is an exacerbated response of the immune system against non-self-proteins called allergens and is typically characterized by biased type-2 T helper cell and deleterious IgE mediated immune responses. The allergic cascade starts with the recognition of allergens by antigen presenting cells, mainly dendritic cells (DCs), leading to Th2 polarization, switching to IgE production by B cells, culminating in mast cell sensitization and triggering. DCs have been demonstrated to play a crucial role in orchestrating allergic diseases. Using different C-type lectin receptors DCs are able to recognize and internalize a number of allergens from diverse sources leading to sensitization. Furthermore, there is increasing evidence highlighting the role of epithelial cells in triggering and modulating immune responses to allergens. As well as providing a physical barrier, epithelial cells can interact with allergens and influence DCs behavior through the release of a number of Th2 promoting cytokines. In this review we will summarize current understanding of how allergens are recognized by DCs and epithelial cells and what are the consequences of such interaction in the context of allergic sensitization and downstream events leading to allergic inflammation. Better understanding of the molecular mechanisms of allergen recognition and associated signaling pathways could enable developing more effective therapeutic strategies that target the initial steps of allergic sensitization hence hindering development or progression of allergic diseases.
过敏是免疫系统对称为过敏原的非自身蛋白质的过度反应,其典型特征是偏向2型辅助性T细胞和有害的IgE介导的免疫反应。过敏反应级联始于抗原呈递细胞(主要是树突状细胞,即DCs)识别过敏原,导致Th2极化,进而B细胞转换为产生IgE,最终导致肥大细胞致敏和触发。已证明DCs在协调过敏性疾病中起关键作用。通过不同的C型凝集素受体,DCs能够识别并内化多种来源的多种过敏原,从而导致致敏。此外,越来越多的证据突出了上皮细胞在触发和调节对过敏原的免疫反应中的作用。上皮细胞除了提供物理屏障外,还可以与过敏原相互作用,并通过释放多种促进Th2的细胞因子来影响DCs的行为。在这篇综述中,我们将总结目前对DCs和上皮细胞如何识别过敏原以及在过敏致敏和导致过敏性炎症的下游事件的背景下这种相互作用的后果的理解。更好地理解过敏原识别的分子机制和相关信号通路可以开发出更有效的治疗策略,这些策略针对过敏致敏的初始步骤,从而阻碍过敏性疾病的发展或进展。