CD200 is a cell surface glycoprotein that functions as an immunoregulatory molecule by engaging CD200 receptors (CD200R) on myeloid cells to suppress inflammatory responses. Primary function: CD200 negatively regulates immune cell activation through CD200R signaling, which dampens macrophage and microglia-mediated inflammatory responses 12. Mechanism: CD200-CD200R interaction induces downstream signaling through Dok2 phosphorylation while suppressing NF-κB activation 3. This engagement reduces production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and suppresses macrophage-mediated cytotoxicity and phagocytosis 14. Disease relevance: Dysregulation of CD200-CD200R signaling contributes to multiple pathologies. In pancreatic cancer, CD200 expression promotes myeloid-derived suppressor cell (MDSC) expansion, creating immunosuppression that limits checkpoint immunotherapy efficacy 5. In diabetic retinopathy, dysregulated CD200 signaling enhances microglial activation and neuronal damage 2. CD200 expression is dysregulated in asthma pathogenesis 6. Clinical significance: CD200 blockade enhances anti-tumor immunity and synergizes with PD-1 checkpoint inhibitors in pancreatic cancer 5. CD200R antagonism attenuates diabetic retinopathy progression 2. During inflammatory resolution, pro-resolving CD200+ fibroblasts stabilize type 2 immune responses 4, suggesting CD200 manipulation could promote healing.