Cell surface glycoprotein CD200 receptor 1 (CD200R1)

Cell surface glycoprotein CD200 receptor 1 (CD200R1) is an inhibitory receptor primarily expressed on myeloid lineage cells (macrophages, dendritic cells, neutrophils) and some T cells. It has two extracellular immunoglobulin-like domains and is activated by its ligand CD200, a broadly expressed membrane glycoprotein. The CD200-CD200R1 interaction results in inhibitory signaling, suppressing the release of proinflammatory cytokines (including TNF-α, interferons, iNOS) and dampening immune responses. This pathway serves as an immune checkpoint, limiting excess inflammation and maintaining self-tolerance. In cancer, the axis suppresses anti-tumor immunity. In the CNS, it regulates microglia activity and prevents neuroinflammation. The mechanism involves phosphorylation of tyrosine residues within the NPxY motif in CD200R1, recruitment of adapter proteins (DOK-1, DOK-2), and downstream inhibition of MAPK/ERK pathways. Pathogens can exploit this receptor for immune evasion. Blocking the interaction is under exploration for immunotherapy, but there are safety concerns regarding immune overactivation and autoimmunity[1][3][4][5][6][7][8].

Other names

CD200R1OX2 receptorCD200 inhibitory receptorOX2R

Blocking CD200-CD200R1 interaction to re-activate suppressed immune responses in cancer or infection\nAntagonism of receptor function to restore cytokine secretion, immune cell activation