CD200, a cell surface glycoprotein, is an immunoregulatory ligand. It interacts with its receptor CD200R, and this interaction is involved in regulating immune responses, playing a significant role in maintaining immune homeostasis. The CD200-CD200R pathway has been associated with multiple biological processes and diseases, including inflammation, transplant rejection, and cancer [2].

In pancreatic ductal adenocarcinoma (PDAC), CD200 is expressed in the tumor microenvironment, and myeloid-derived suppressor cells (MDSC) from PDAC patients show elevated CD200R expression. In vivo antibody blocking of CD200 in mouse models limited tumor progression, reduced intratumoral MDSC percentage, and enhanced the efficacy of PD-1 checkpoint antibodies, indicating that CD200 promotes immunosuppression in the PDAC microenvironment [1]. In a type I diabetes mouse model, targeting CD200R in vivo prevented visual dysfunction, microglia activation, and retinal inflammation, as CD200-CD200R signaling between amacrine cells and microglia is dysregulated during early diabetic retinopathy [3].

In conclusion, CD200 is crucial in immunoregulation. Mouse models, such as those with in vivo antibody-mediated CD200 blockade in PDAC and targeting of CD200R in diabetes-related retinopathy, have revealed its role in promoting immunosuppression in the tumor microenvironment and in the pathogenesis of early diabetic retinopathy. These findings suggest that CD200-targeted therapies could be promising for treating certain cancers and diabetic retinopathy [1,3].

References:

1. Choueiry, Fouad, Torok, Molly, Shakya, Reena, Carson, William E, Mace, Thomas A. 2020. CD200 promotes immunosuppression in the pancreatic tumor microenvironment. In Journal for immunotherapy of cancer, 8, . doi:10.1136/jitc-2019-000189. https://pubmed.ncbi.nlm.nih.gov/32581043/

2. Kotwica-Mojzych, Katarzyna, Jodłowska-Jędrych, Barbara, Mojzych, Mariusz. 2021. CD200:CD200R Interactions and Their Importance in Immunoregulation. In International journal of molecular sciences, 22, . doi:10.3390/ijms22041602. https://pubmed.ncbi.nlm.nih.gov/33562512/

3. Pfeifer, Charles W, Walsh, James T, Santeford, Andrea, Ruzycki, Philip A, Apte, Rajendra S. 2023. Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2308214120. doi:10.1073/pnas.2308214120. https://pubmed.ncbi.nlm.nih.gov/37903272/