Disease relevance of CD200R1

• Here, we show that the product of the K14 open reading frame from human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) interacts with human CD200R and is expressed at the surfaces of infected cells solely during the lytic cycle [1].
• Collectively, these findings suggest that orexins stimulate catecholamine secretion from human pheochromocytomas, acting through OX2-R coupled to the PLC-PKC signaling pathway [2].
• Forskolin-stimulated cyclic adenosine 3,5-monophosphate (cAMP) accumulation in OX2R-expressing cells was inhibited by orexin in a dose-dependent manner, and the effect was abolished by pretreatment with pertussis toxin (PTX) [3].
• The risk of cluster headache (CH) is associated with the G-allele of the G1246A polymorphism in the hypocretin receptor 2 (HCRTR2) gene [4].
• All adenomas expressed OX1-R and OX2-R mRNAs, and real-time PCR showed that the expression of both receptors was up-regulated in adenomas, compared with normal adrenal cortex [5].

Psychiatry related information on CD200R1

• It remains unclear if autoantibodies against hypocretin receptors (hcrtrl and hcrtr2) are involved in narcolepsy [6].
• However, hypocretin-1 had no effect on cataplexy or wakefulness in hypocretin receptor-2 gene (Hcrtr2) mutated narcoleptic Dobermans [7].

High impact information on CD200R1

• CD200 is a membrane glycoprotein that imparts an immunoregulatory signal through CD200R, leading to the suppression of T-cell-mediated immune responses [8].
• We found that human CD200R is predominantly expressed on basophils in amounts higher than on other human peripheral blood leukocytes [9].
• Is the CD200/CD200 receptor interaction more than just a myeloid cell inhibitory signal [10]?
• METHODS: We performed association studies on the insertion/deletion (I/D) sequence polymorphism of ACE and single nucleotide polymorphisms within the prepro-orexin (HCRT), orexin receptor 1 (HCRTR1), and orexin receptor 2 (HCRTR2) genes [11].
• OXA-immunoreactive cells in the islets of Langerhans contained insulin with a subset expressing OX2R [12].

Biological context of CD200R1

• Using the canine model, we investigated ( 1 ) whether hypocretin deficiency is involved in sporadic cases and ( 2 ) whether alterations in hypocretin neurons or ligand levels also contribute to the phenotype in Hcrtr 2 mutants [13].
• No relationship was found between narcolepsy and DLA in Hcrtr2-mediated narcolepsy but loose genetic linkage was observed (Zmax=2.3 at theta=25%, m= 40) [14].
• Recent studies have linked the development of autosomal recessive canine narcolepsy to a disruption of the hypocretin receptor 2 (Hcrtr2) gene on the same chromosome as the canine MHC region (CFA12), but not close to the DLA [14].
• The expression of both HCRTR2 and MEF2C in the peripheral blood was validated by reverse transcription PCR [15].
• Gene expression for OX1R and OX2R in central and peripheral tissues was analysed using quantitative real time RT-PCR [16].

Anatomical context of CD200R1

• In order to establish protein array technology for the characterization of the weak interactions between leukocyte membrane proteins, we selected the human leukocyte membrane protein CD200 (OX2) and its cell surface receptor (hCD200R) as a model system [17].
• Because monocytic myeloid cells provide a link between the innate and adaptive immune response, mechanisms to control their function through receptors such as CD200R will have therapeutic potential [10].
• Spleen expresses cell surface CD200R1, while bone marrow shows predominantly expression of cell surface CD200R2/R3 [18].
• High levels of OX1-R mRNA and low levels of OX2-R mRNA have been previously detected in the human adrenal cortex and medulla [2].
• Protein expression of both OR receptors in human testis was confirmed by Western blotting analysis, with apparent molecular masses of 50 kDa for OX1R and 40 kDa for OX2R [19].

Associations of CD200R1 with chemical compounds

• CD200 (OX2) is a broadly distributed cell surface glycoprotein that interacts with a receptor on myeloid cells (CD200R) involved in regulation of macrophage function [20].
• We found a significant decrease in histamine content in the cortex and thalamus, two structures important for histamine-mediated cortical arousal, in Hcrtr-2 mutated narcoleptic Dobermans [21].
• While the HCRTR2 1246G allele was significantly associated with CH in this group, treatment outcomes with triptans, oxygen, verapamil and corticosteroids remained unaffected [4].
• By the double immunofluorescence techniques, we demonstrated that virtually all medullar cells (epinephrine and norepinephrine cells) expressed OX2R [22].

Physical interactions of CD200R1

• We report the first characterization of human CD200R (hCD200R) and define its binding characteristics to hCD200 [23].

Regulatory relationships of CD200R1

• CONCLUSIONS: We conclude that CD200 triggering of bone-marrow DCs in the absence of CD200R1 engagement induces CD4(+)CD25(+) Treg, and these cloned antigen-specific Treg may have clinical utility [18].

Other interactions of CD200R1

• BACKGROUND: CD200 delivers an immunsuppressive signal that augments allograft survival following interaction with its receptor, CD200R1 [24].
• CD200 receptor and fractalkine receptor stimulation was achieved by addition to explants of CD200:Fc fusion protein and recombinant cytokine respectively, with or without LPS-IFNgamma stimulation that is known to suppress migration [25].
• Detection of autoantibodies against hypocretin, hcrtrl, and hcrtr2 in narcolepsy: anti-Hcrt system antibody in narcolepsy [6].
• Orexins orchestrate their actions by binding and activating two types of G protein-coupled receptors, OR-1 receptor (OX1R) and OR-2 receptor (OX2R) [19].

Analytical, diagnostic and therapeutic context of CD200R1

• Site-directed mutagenesis of CD200R showed that, like CD200, it interacted through its N-terminal domain [20].
• Here we demonstrated by RT-PCR the expression of the OX2-R, but not the OX1-R, gene in 10 benign secreting pheochromocytomas [2].
• The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease [26].
• Bone marrow transplantation between two DLA identical affected (Hcrtr2-/-) and unaffected (Hcrtr2+/-) siblings was also performed and found not to be successful neither in transmitting narcolepsy nor in relieving the symptoms in Doberman pinschers [14].

References