Zhou Yihan, Jiang Shisong
Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ, UK.
Pathogens. 2023 Jun 8;12(6):817. doi: 10.3390/pathogens12060817.
The immune system is a complex network of multiple cells, tissues, and organs that protects the body against foreign pathogenic invaders. However, the immune system may mistakenly attack healthy cells and tissues due to the cross-reactivity of anti-pathogen immunity, leading to autoimmunity by autoreactive T cells and/or autoantibody-secreting B cells. Autoantibodies can accumulate, resulting in tissue or organ damage. The neonatal crystallizable fragment receptor (FcRn) is an important factor in immune regulation through controlling the trafficking and recycling of immunoglobulin G (IgG) molecules, the most abundant antibody in humoral immunity. In addition to its role in IgG trafficking and recycling, FcRn is also involved in antigen presentation, which is a crucial step in the activation of the adaptive immune response via directing the internalization and trafficking of antigen-bound IgG immune complexes into compartments of degradation and presentation in antigen-presenting cells. Efgartigimod, an FcRn inhibitor, has shown promise in reducing the levels of autoantibodies and alleviating the autoimmune severity of myasthenia gravis, primary immune thrombocytopenia, and pemphigus vulgaris/foliaceus. This article aims to provide an overview of the importance of FcRn in antigen-presenting cells and its potential as a therapeutic target in autoimmune diseases, using efgartigimod as an example.
免疫系统是一个由多种细胞、组织和器官组成的复杂网络，它保护身体免受外来致病入侵者的侵害。然而，由于抗病原体免疫的交叉反应性，免疫系统可能会错误地攻击健康细胞和组织，导致自身反应性T细胞和/或分泌自身抗体的B细胞引发自身免疫。自身抗体可能会积累，导致组织或器官损伤。新生儿可结晶片段受体（FcRn）是免疫调节中的一个重要因素，它通过控制体液免疫中最丰富的抗体——免疫球蛋白G（IgG）分子的运输和循环来发挥作用。除了在IgG运输和循环中的作用外，FcRn还参与抗原呈递，这是通过将与抗原结合的IgG免疫复合物内化并运输到抗原呈递细胞中的降解和呈递区室，从而激活适应性免疫反应的关键步骤。FcRn抑制剂艾加莫德已显示出有望降低自身抗体水平，并减轻重症肌无力、原发性免疫性血小板减少症和寻常型/落叶型天疱疮的自身免疫严重程度。本文旨在以艾加莫德为例，概述FcRn在抗原呈递细胞中的重要性及其作为自身免疫性疾病治疗靶点的潜力。
