Characterization of the CD200 Receptor Family in Mice and Humans and Their Interactions with CD200

Abstract

CD200 (OX2) is a broadly distributed cell surface glycoprotein that interacts with a structurally related receptor (CD200R) expressed on rodent myeloid cells and is involved in regulation of macrophage function. We report the first characterization of human CD200R (hCD200R) and define its binding characteristics to hCD200. We also report the identification of a closely related gene to hCD200R, designated hCD200RLa, and four mouse CD200R-related genes (termed mCD200RLa-d). CD200, CD200R, and CD200R-related genes were closely linked in humans and mice, suggesting that these genes arose by gene duplication. The distributions of the receptor genes were determined by quantitative RT-PCR, and protein expression was confirmed by a set of novel mAbs. The distribution of mouse and human CD200R was similar, with strongest labeling of macrophages and neutrophils, but also other leukocytes, including monocytes, mast cells, and T lymphocytes. Two mCD200 receptor-like family members, designated mCD200RLa and mCD200RLb, were shown to pair with the activatory adaptor protein, DAP12, suggesting that these receptors would transmit strong activating signals in contrast to the apparent inhibitory signal delivered by triggering the CD200R. Despite substantial sequence homology with mCD200R, mCD200RLa and mCD200RLb did not bind mCD200, and presently have unknown ligands. The CD200 receptor gene family resembles the signal regulatory proteins and killer Ig-related receptors in having receptor family members with potential activatory and inhibitory functions that may play important roles in immune regulation and balance. Because manipulation of the CD200-CD200R interaction affects the outcome of rodent disease models, targeting of this pathway may have therapeutic utility.

Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic arthritis

“…Conversely, RA SF abrogated the expression of CD163, even in the presence of the M2-polarizing factor IL-10 ( Figures 1A and B). These data were confirmed by the expression pattern of CD200R, an inhibitory macrophage receptor that is down-regulated during classic macrophage activation (16,17). The expression of CD200R was up-regulated by SpA SF but suppressed by maturation in the presence of RA SF ( Figure 1C).…”

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

“…[21]. It also resembles these interactions in that both receptor and ligand are relatively closely related to each other, are located on a small region of the chromosome and are likely to have arisen by gene duplication and evolved from a homophilic interaction [3]. At the molecular level, the finding that CD200 and CD200R interact through the GFCC' faces of their N-terminal domains is similar to the CD2/CD58 interaction [22] and the junctional adhesion molecule-1 (JAM1) homotypic interaction [23].…”

“…It interacts with a receptor termed CD200R (reviewed in [1]) that is expressed mainly on myeloid cells [2] but also on some lymphocytes [3]. Functional analysis of the CD200-knockout mice [4] shows a phenotype in myeloid cells consistent with CD200 giving an inhibitory signal through CD200R.…”

The inhibitory CD200R is differentially expressed on human and mouse T and B lymphocytes

“…Lack of CD200R signalling in CD200 −/− mice was found to result in enhanced Th2 switching upon induction of tolerance, implicating a role for CD200R signalling in regulating Th2 cell function (Taylor et al, 2005). Moreover, expression of CD200R on lymphocyte subsets was shown, suggesting a broader role for CD200R in the regulation of immune cells (Wright et al, 2003;Rosenblum et al, 2005). Indeed, CD3-induced proliferation and cytokine secretion by dendritic epidermal T cells can be inhibited by crosslinking of CD200R on the surface of these cells (Rosenblum et al, 2005).…”

“…CD200R has been reported to be mainly expressed on myeloid cells such as monocytes, macrophages, granulocytes and dendritic cells and is an important signalling molecule in the inhibition of myeloid responses to challenge (Wright et al, , 2003. In vitro studies have shown that ligation of CD200R results in decreased degranulation and cytokine secretion by mast cells, monocytes and macrophages (Jenmalm et al, 2006;Cherwinski et al, 2005).…”