Transcriptional control of complement receptor gene expression

Abstract

Immune complement is a critical system in the immune response and protection of host cells from damage by complement is critical during inflammation. The expression of the receptors for the inflammatory anaphylatoxin molecules is also key in immunity. In order to fully appreciate the biology of complement, a basic understanding of the molecular regulation of complement receptor gene expression is critical, yet these kinds of studies are lacking for many genes. Importantly, recent genetic studies have demonstrated that promoter-enhancer polymorphisms can contribute to pathology in diseases such as atypical hemolytic uremic syndrome. This review will focus on what is currently known about the genetic regulation of key protective complement receptors genes including CR1 (CD35), CR2 (CD21), Crry, MCP (CD46), DAF (CD55), and CD59. In addition, the regulation of the anaphylatoxin receptors genes, C3aR and C5aR (CD88) will also be discussed. Since new research continuously uncovers novel functions for these proteins, a greater appreciation of the mechanisms involved in gene regulation will be critical for understanding the biology of these molecules.

Complement Factor H Deficiency Results in Decreased Neuroretinal Expression ofCd59ain Aged Mice

“…Together, the reports do support a tissuespecific regulation of CD59, which may be a consequence of complex control at the transcriptional level. 33 Although the total loss of CFH-function in Cfh À/À mice does not accurately reflect the relative loss of function in the AMD risk-conferring CFH Y402H genotype, similarities have been reported. As such, it was shown that RPE from donors with the CFH HH402 genotype had a tendency to decreased expression of CD59 compared with RPE from the CFH YY402 donors, 18 FIGURE 3.…”

Murine BAFF-receptor residues 168–175 are essential for optimal CD21/35 expression but dispensable for B cell survival

“…Dependence of Cr2 gene expression on NF-κB2 pathway activation has not been reported (Martin, 2007). BAFF might regulate CD21/35 expression and survival independently, since a brief blockade of BAFF in vivo reduced CD21/35 expression without reducing B cell survival (Gorelik et al, 2004).…”

Complement Activation in the Central Nervous System: A Biophysical Model for Immune Dysregulation in the Disease State

“…We hypothesize that mutations in CR1 handicap its ability to deactivate C3b, and the end result is loss of protection to essential brain cells from immune-mediated clearance. The normal number of CR1 receptors on a neuron is unknown, but cell surface CR1 has been characterized on blood plasma cells: only 100-1200 copies on red blood cells and ∼20,00-50,000 on nucleated cells of the immune system (Martin, 2007), so even a small disruption of CR1 functional capacity or structural stability could have significant deleterious effect. In contrast, a more abundant receptor such as CR3 is present on the cell surface in 100,000-200,000 copies (Abbas et al, 2019).…”