CD200/CD200R Paired Potent Inhibitory Molecules Regulating Immune and Inflammatory Responses; part I: CD200/CD200R Structure, Activation, and Function

Abstract

Summary: cd200/cd200R are highly conserved type i paired membrane glycoproteins that belong to the ig superfamily containing a two immunoglobulin -like domain (v, c). cd200 is broadly distributed in a variety of cell types, whereas CD200R is primarily expressed in myeloid and lymphoid cells. They fulfill multiple functions in regulating inflammation. the interaction between cd200/cd200R results in activation of the intracellular inhibitory pathway with Rasgap recruitment and thus contributes to effector cell inhibition. It was confirmed that the CD200R activation stimulates the differentiation of t cells to the treg subset, upregulates indoleamine 2,3 -dioxygenase activity, modulates cytokine environment from a Th1 to a Th2 pattern, and facilitates an antiinflammatory IL -10 and TGF -β synthesis. CD200/CD200R are required for maintaining self -tolerance. Many studies have demonstrated the importance of cd200 in controlling autoimmunity, inflammation, the development and spread of cancer, hypersensitivity, and spontaneous fetal loss.

Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells

“…In opposition to the results obtained for T-bet mRNA expression, MSCs support to Treg (CD4 + FoxP3 + ) induction and expansion is widely described in the literature, contributing for this occurrence PGE2, TGF-β, HLA-G5, IDO, LIF, IL-10 and CD200, whose expression increases after MSCs exposure to pro-inflammatory factors [34,57,59,63,70,75,76,79],[89,100-106]. …”

“…These capabilities are, at least in part, mediated by soluble factors produced by MSCs [63,69], namely TGF-β [70], PGE2 [59,71-73], IDO [59,74,75], leukemia inhibitory factor (LIF) [76], HLA-G5 [59,77-79], galectin [77,80-83], Jagged-1 [84], adenosine [85,86] and semaphorin-3A [80,87], and/or cellular contact and interaction between the MSCs’ surface proteins HLA-G1 [78,88], PD-L1 [28], CD200 [89,90] and B7-H4 [91-93], and the respective receptors on T cells.…”

Th1/Th2 PB balance and CD200 expression of patients with active severe alopecia areata

“…It is also expressed in the central nervous system, testis, ovary and other immune organs (10) by the interaction with the receptor CD200R. It lowers the activity of myeloid cells, regulates immune response threshold value, regulates and controls cytokines to produce polarity (Th1/Th2 equilibrium), and participated in maintaining the immunity homeostasis of the body, specific tissues and organs (11). CD200 can be expressed with the hair follicle stem cell markers K14, 15 and 19, which makes it important in identifying and sorting hair follicle stem cells (12).…”

F4/80+Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor EngraftmentIn Vivo

“…We hypothesize that macrophage recruitment and phagocytosis of ESHPs may be related to three aspects of their maturation state: (1) ESHPs secrete products that recruit monocytes and macrophages or induce differentiation or proliferation of macrophages [27], (2) ESHPs express activating ligands [31, 32], and/or (3) ESHPs lack macrophage inhibitory ligands [33–37]. With regard to the latter point, major histocompatibility complex class I (MHC-I) has been characterized as a macrophage inhibitory ligand [29, 38], and ESHPs express MHC-I at moderate levels compared to adult hematopoietic cells [21].…”