Sepúlveda-Delgado Jesús, Llorente Luis, Hernández-Doño Susana
Research Division, Servicios de Salud IMSS BIENESTAR, Hospital Regional de Alta Especialidad Ciudad Salud, Tapachula 30700, Mexico.
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14000, Mexico.
Int J Mol Sci. 2025 Feb 21;26(5):1851. doi: 10.3390/ijms26051851.
Receptors for the immunoglobulin G constant fraction (FcγRs) are widely expressed in cells of the immune system. Complement-independent phagocytosis prompted FcγR research to show that the engagement of IgG immune complexes with FcγRs triggers a variety of cell host immune responses, such as phagocytosis, antibody-dependent cell cytotoxicity, and NETosis, among others. However, variants of these receptors have been implicated in the development of and susceptibility to autoimmune diseases such as systemic lupus erythematosus. Currently, the knowledge of FcγR variants is a required field of antibody therapeutics, which includes the engineering of recombinant soluble human Fc gamma receptors, enhancing the inhibitory and blocking the activating FcγRs function, vaccines, and organ transplantation. Importantly, recent interest in FcγRs is the antibody-dependent enhancement (ADE), a mechanism by which the pathogenesis of certain viral infections is enhanced. ADEs may be responsible for the severity of the SARS-CoV-2 infection. Therefore, FcγRs have become a current research topic. Therefore, this review briefly describes some of the historical knowledge about the FcγR type I family in humans, including the structure, affinity, and mechanism of ligand binding, FcγRs in diseases such as systemic lupus erythematosus (SLE), and the potential therapeutic approaches related to these receptors in SLE.
免疫球蛋白G恒定区片段受体（FcγRs）在免疫系统细胞中广泛表达。不依赖补体的吞噬作用推动了FcγR研究，结果表明IgG免疫复合物与FcγRs的结合会引发多种细胞宿主免疫反应，如吞噬作用、抗体依赖性细胞毒性和中性粒细胞胞外陷阱形成等。然而，这些受体的变体与自身免疫性疾病（如系统性红斑狼疮）的发生发展和易感性有关。目前，FcγR变体的知识是抗体治疗学的一个必要领域，其中包括重组可溶性人Fcγ受体的工程改造、增强抑制性和阻断激活FcγRs的功能、疫苗以及器官移植。重要的是，最近对FcγRs的关注在于抗体依赖性增强（ADE），这是一种增强某些病毒感染发病机制的机制。ADE可能是导致SARS-CoV-2感染严重程度的原因。因此，FcγRs已成为当前的研究热点。因此，本综述简要描述了一些关于人类FcγR I型家族的历史知识，包括结构、亲和力和配体结合机制、系统性红斑狼疮（SLE）等疾病中的FcγRs，以及SLE中与这些受体相关的潜在治疗方法。
