Holtrop Tosca, Budding Kevin, Brandsma Arianne M, Leusen Jeanette H W
Immunotherapy Laboratory, Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, The Netherlands.
Immunother Adv. 2022 May 28;2(1):ltac011. doi: 10.1093/immadv/ltac011. eCollection 2022.
The Fc gamma receptor I (FcγRI or CD64) is the only human Fc receptor with a high affinity for monomeric IgG. It plays a crucial role in immunity, as it mediates cellular effector functions of antibodies including phagocytosis, antigen presentation, and cytokine production. FcγRI is constitutively saturated with monomeric IgG and this feeds the dogma that it has no role in immune responses. However, recent findings have implicated a role for FcγRI in various autoimmune disorders, neuropathies, and antibody therapy in tumor models. By a process known as 'inside-out' signaling, stimulation of myeloid cells with cytokines such as tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) enhances FcγRI binding to immune complexes (ICs), including antibody-opsonized pathogens or tumor cells. This review focuses on the current knowledge on interaction of FcγRI with IgG and ICs and the effect of inside-out signaling on FcγRI functioning. Additionally, this review will address potential clinical applications of targeting FcγRI, and the tools that can be used to overcome IC-mediated autoimmune diseases on the one hand, and to enhance antibody-based anti-cancer therapy on the other.
Fcγ受体I（FcγRI或CD64）是唯一对单体IgG具有高亲和力的人Fc受体。它在免疫中起关键作用，因为它介导抗体的细胞效应功能，包括吞噬作用、抗原呈递和细胞因子产生。FcγRI持续被单体IgG饱和，这导致了一种观点，即它在免疫反应中不起作用。然而，最近的研究结果表明FcγRI在各种自身免疫性疾病、神经病变以及肿瘤模型的抗体治疗中发挥作用。通过一种称为“由内向外”信号传导的过程，用肿瘤坏死因子α（TNF-α）和干扰素-γ（IFN-γ）等细胞因子刺激髓样细胞可增强FcγRI与免疫复合物（ICs）的结合，包括抗体调理的病原体或肿瘤细胞。本综述重点关注FcγRI与IgG和ICs相互作用的现有知识，以及由内向外信号传导对FcγRI功能的影响。此外，本综述还将探讨靶向FcγRI的潜在临床应用，以及一方面可用于克服IC介导的自身免疫性疾病、另一方面可用于增强基于抗体的抗癌治疗的工具。
