The Diverse Functions of the Ubiquitous Fcγ Receptors and Their Unique Constituent, FcRγ Subunit

Abstract

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.

Adaptive Subsets Limit the Anti-Tumoral NK-Cell Activity in Hepatocellular Carcinoma

“…The decreased immunoregulatory function of adaptive CD56 dim NK cells may result from the low NCR expression. This is in line with previous reports in the LCMV mouse system [55][56][57], showing, for example, that an altered regulation of CD8 + T cells by NK cells in FcεRIγ -/mice resulted in better survival. However, it remains unclear whether the FcεRIγ -/-NK cells in this mouse model are comparable to their human counterparts since, in the murine system, adaptive/memory-like NK cells are defined by other features such as Ly49H expression.…”

Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

“…FcRγ is often referred to as FcεRIγ since it was first discovered as the third subunit of FcεRI [130]. Later, it was revealed that it is a common subunit of various FcRs and is also able to associate with a number of immune receptors such as blood dendritic cell antigen 2 (BDCA2) and immunoglobulin-like transcript 7 (ILT7) [131].…”

Neutrophils and Influenza: A Thin Line between Helpful and Harmful

“…Murine neutrophils express all FcγR subtypes, of which, FcγRI, FcγRIII, and FcγRIV are activating receptors and FcγRIIB is the sole inhibitory receptor; although levels of FcγRI are reported to be low [23]. In contrast, human neutrophils constitutively express the activating receptors FcγRIIA and FcγRIIIB, in addition to the inhibitory receptor FcγRIIB; expression of FcγRI expression is inducible [23,24]. Furthermore, FcαRI, an activating receptor which binds immunoglobulin A (IgA), is highly expressed on human neutrophils.…”