Hamdan Thamer A, Lang Philipp A, Lang Karl S
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
Pathogens. 2020 Feb 20;9(2):140. doi: 10.3390/pathogens9020140.
Fc gamma receptors (FcγRs) are widely expressed on a variety of immune cells and play a myriad of regulatory roles in the immune system because of their structural diversity. Apart from their indispensable role in specific binding to the Fc portion of antibody subsets, FcγRs manifest diverse biological functions upon binding to their putative ligands. Examples of such manifestation include phagocytosis, presentation of antigens, mediation of antibody-dependent cellular cytotoxicity, anaphylactic reactions, and the promotion of apoptosis of T cells and natural killer cells. Functionally, the equilibrium between activating and inhibiting FcγR maintains the balance between afferent and efferent immunity. The γ subunit of the immunoglobulin Fc receptor (FcRγ) is a key component of discrete immune receptors and Fc receptors including the FcγR family. Furthermore, FcγRs exert a key role in terms of crosslinking the innate and adaptive workhorses of immunity. Ablation of one of these receptors might positively or negatively influence the immune response. Very recently, we discovered that FcRγ derived from natural cytotoxicity triggering receptor 1 (NCR1) curtails CD8 T cell expansion and thereby turns an acute viral infection into a chronic one. Such a finding opens a new avenue for targeting the FcγRs as one of the therapeutic regimens to boost the immune response. This review highlights the structural heterogeneity and functional diversity of the ubiquitous FcγRs along with their featured subunit, FcRγ.
Fcγ受体(FcγRs)广泛表达于多种免疫细胞上,由于其结构多样性,在免疫系统中发挥着众多调节作用。除了在特异性结合抗体亚群的Fc部分中发挥不可或缺的作用外,FcγRs在与假定配体结合后还表现出多种生物学功能。这种表现的例子包括吞噬作用、抗原呈递、抗体依赖性细胞毒性的介导、过敏反应以及促进T细胞和自然杀伤细胞的凋亡。在功能上,激活型和抑制型FcγR之间的平衡维持了传入免疫和传出免疫之间的平衡。免疫球蛋白Fc受体(FcRγ)的γ亚基是包括FcγR家族在内的离散免疫受体和Fc受体的关键组成部分。此外,FcγRs在连接先天性和适应性免疫主力军方面发挥着关键作用。这些受体中的任何一个缺失都可能对免疫反应产生正向或负向影响。最近,我们发现源自自然细胞毒性触发受体1(NCR1)的FcRγ会抑制CD8 T细胞的扩增,从而将急性病毒感染转变为慢性感染。这一发现为将FcγRs作为增强免疫反应的治疗方案之一提供了一条新途径。本综述重点介绍了普遍存在的FcγRs及其特色亚基FcRγ的结构异质性和功能多样性。