CD200CD200R

CD200CD200R refers to the ligand-receptor pair formed by CD200 (also called OX2) and its receptor CD200R. This axis modulates immune responses by delivering inhibitory signals that help maintain immune tolerance and regulate inflammation. CD200 is a broadly expressed type I transmembrane glycoprotein found on neurons, endothelial and epithelial cells, B cells, and other cell types. Its receptor, CD200R, is predominantly expressed on myeloid cells such as macrophages and dendritic cells, with additional expression on some lymphocytes.

Binding of CD200 to CD200R activates signaling motifs in the receptor’s cytoplasmic tail, typically immunoreceptor tyrosine-based inhibitory motifs that recruit phosphatases such as SHP-1 and SHP-2. This signaling dampens cellular activation, leading to reduced production of pro-inflammatory cytokines, diminished antigen presentation, and lowered phagocytic and co-stimulatory activity. In the central nervous system, neuronal CD200 can restrain microglial activation through CD200R, contributing to tissue homeostasis.

Biological roles of the CD200CD200R axis include maintenance of self-tolerance, control of inflammatory responses, and involvement in transplantation tolerance. Some tumors exploit the axis to evade immune surveillance by upregulating CD200. Conversely, therapeutic strategies that engage CD200R or block CD200 can modulate immunity: agonists of CD200R are explored for autoimmune and inflammatory conditions, while antagonists may enhance anti-tumor immunity. Several CD200R family receptors exist, with CD200R1 being the principal inhibitory receptor in humans.

Research tools include CD200 or CD200R knockout models, and soluble CD200-Fc fusion proteins used to study function and therapeutic potential.