CD200-CD200R paired potent inhibitory molecules regulating immune and inflammatory responses; part I: CD200/CD200R structure, activation, and function
Abstract
CD200/CD200R are highly conserved type I paired membrane glycoproteins that belong to Ig superfamily, containing two immunoglobulin-like domain (V, C). CD200 is broadly distributed on a variety of cell types, whereas CD200R is primarily expressed on myeloid and lymphoid cells.
They fulfill multiple functions in tuning of inflammation. The interaction between CD200/CD200R results in activation of the intracellular inhibitory pathway with RasGAP recruitment and thus contributes to effector cells inhibition.
It was confirmed that the CD200R activation stimulates differentiation of T cells to the Treg subset, upregulates indoleamine 2,3-dioxygenase activity, modulates cytokine environment from Th1 to Th2 pattern, potentiate an antiinflammatory IL-10 and TGF-β synthesis. CD200/CD200R are required for maintaining self-tolerance.
Many studies demonstrated the importance of CD200 in controlling autoimmunity, inflammation, development and spread of cancer, hypersensitivity, and spontaneous fetal loss.