Presence and possible impact of Fcγ receptors on resident kidney cells in health and disease

Abstract

Fcγ receptors (FcγRs) bind the Fc fragment of immunoglobulin G (IgG), mostly after IgG opsonizes a bacterial or viral antigen or danger/damage‐associated molecule. Consequently, classic FcγRs initiate phagocytosis of the IgG–antigen immune complex and stimulate an immune reaction against the threat. Signals from activating FcγRs (FcγRI, FcγRIIa/c, FcγRIIIa/b) are balanced by inhibitory FcγRIIb and likely also by two FcR‐like proteins (FCRL4 and FCRL5). The neonatal Fc receptor (FcRn) recirculates IgG and increases its half‐life. The last FcγR that has been identified in humans, tripartite motif‐containing protein 21 (TRIM21), acts toward pathogen destruction via the proteasomal or autophagic pathway. The expression of FcγRs occurs almost exclusively in immune cells. However, podocytes, key cells in the glomerular filtration barrier, also possess several features of an immune cell and express receptors for IgG. The presence of FcγRs in glomeruli was analyzed in the Human Protein Atlas project. FcγR occurrence in whole glomeruli or in particular resident kidney cells was also showed in a few original articles. In human podocytes only FcRn has been studied extensively, and the presence and role of other FcγRs remain obscure. Research on the genetic background of kidney diseases revealed a connection between FcγRs and several nephropathies. Investigations of FcγR expression in podocytes appear to be of great clinical importance. The present review discusses the latest literature on FcγRs in kidney cells (especially podocytes), with an emphasis on their involvement in kidney health and disease.

Not an immune cell, but they may act like one—cells with immune properties outside the immune system

“…Podocytes produce the neonatal receptor for the Fc fragment of IgG (FcRn) but are unable to initiate the process of phagocytosis, which can be stimulated by classical FcγRs. Despite the assumptions of the presence of classical FcγR on podocytes, 50 it has not been confirmed yet. Podocytes are also able to present foreign antigens to T cells because of the expression of both MHC class I and II molecules and costimulatory CD80/CD86 molecules.…”

A Interacting Model: How TRIM21 Orchestrates with Proteins in Intracellular Immunity

“…[107] TRIM21 was proved to be a unique cytosolic receptor that shows remarkably broad isotype specificity, identified as the last Fc𝛾 receptor (Fc𝛾R) that binds to the Fc region of antibodies, structurally, thermodynamically, and kinetically conserved. [54,108,109] Distinguished from other FcRs that asymmetrically bind one single heavy chain, TRIM21 is a dimeric molecule, containing two PRY/SPRY binding domains, which binds both CH2:CH3 elbow domains in a pincer-like interaction, [110] binding both heavy chains of immunoglobulins simultaneously at equal proportion, suggesting as a new molecular to antibodies detection. [24,111] Clinically, anti-TRIM21/Ro52 antibodies have been found in a wide variety of diseases (Table 1).…”