CD200, a cell surface glycoprotein, is an immunoregulatory ligand that interacts with its receptor CD200R. This interaction plays a crucial role in multiple immunoregulatory pathways, influencing inflammation, transplant rejection, and immune responses in various diseases [2]. CD200 has emerged as a potentially important molecule in understanding the immune system's regulation and its implications in disease development [2]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, can be valuable tools in studying CD200's function.

In pancreatic ductal adenocarcinoma (PDAC), in vivo antibody blocking of CD200 (akin to a functional knockout approach) in MT-5 tumor-bearing mice and KPC-Brca2 mice limited tumor progression and reduced the percentage of intratumoral myeloid-derived suppressor cells (MDSC) [1]. Also, CD200 antibody blockade enhanced the efficacy of PD-1 checkpoint antibodies compared with single-antibody therapies [1]. In a type I diabetes mouse model, targeting CD200R (perturbing the CD200-CD200R signaling) prevented visual dysfunction, microglia activation, and retinal inflammation, indicating its role in early diabetic retinopathy [3].

In conclusion, CD200, through its interaction with CD200R, is a key regulator in the immune system. Model-based research, especially KO/CKO mouse models, has revealed its significant role in diseases like PDAC and early diabetic retinopathy. These findings suggest that CD200 could be a potential target for immunotherapy in cancer and a therapeutic target in early 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/