Cd200r1, the receptor for CD200, is an immune-regulatory cell surface receptor. It is crucial in limiting inflammation through the CD200-CD200R1 inhibitory signaling pathway, which impacts multiple inflammatory pathways. This pathway regulates the expression of pro-inflammatory molecules such as tumor necrosis factor, interferons, and inducible nitric oxide synthase [1].

In a sciatic nerve injury mouse model, blocking CD200R1 with a specific antibody reduced the acute entrance of neutrophils and monocytes from the blood after injury. Long-term, this blockade impaired spontaneous functional recovery, indicating that CD200R1 is important for mounting a successful acute inflammatory reaction and effective functional recovery post-injury [2].

In a mouse model of Cryptococcus neoformans lung infection, CD200R1 blockade enhanced eosinophilia, while agonism reduced it, without completely altering fungal burden. This shows that CD200R1 regulates eosinophilia during pulmonary fungal infection [3].

In stroke mouse models, injection of CD200Fc (a CD200R1 agonist) promoted the anti-inflammatory response and alleviated ischemic injury, suggesting that the CD200-CD200R1 signaling pathway regulates neuroinflammation after stroke [4].

In Parkinson's disease, NFKB1 directly regulates CD200R1. NFKB1 -/- mice showed exacerbated microglia activation and dopaminergic neuron loss after MPTP treatment, indicating the importance of the NFKB1-CD200R1 axis in Parkinson's disease [5].

In aged mice with postoperative cognitive dysfunction (POCD), CD200Fc attenuated neuroinflammation, synaptic deficits, and cognitive impairment, while CD200R1 Ab had the opposite effect, suggesting the CD200/CD200R1 axis modulates POCD via the PI3K/Akt/NF-κB signaling pathway [6].

In psoriasis mouse models, blocking CD200R1 enhanced neutrophil recruitment and psoriasis-like inflammation, highlighting CD200R1 as a potential target to dampen inflammation in psoriasis patients [7].

In conclusion, Cd200r1 plays a vital role in regulating inflammation across various biological processes and disease conditions. Gene-knockout or-blocking studies in mouse models have revealed its significance in nerve injury recovery, pulmonary fungal infection-related eosinophilia regulation, stroke-induced neuroinflammation, Parkinson's disease pathophysiology, postoperative cognitive dysfunction, and psoriasis-associated inflammation. These findings provide potential therapeutic targets for the corresponding diseases.

References:

1. Vaine, Christine A, Soberman, Roy J. . The CD200-CD200R1 inhibitory signaling pathway: immune regulation and host-pathogen interactions. In Advances in immunology, 121, 191-211. doi:10.1016/B978-0-12-800100-4.00005-2. https://pubmed.ncbi.nlm.nih.gov/24388216/

2. Pannunzio, Bruno, Amo-Aparicio, Jesús, Julián, Camila, Peluffo, Hugo, Lago, Natalia. 2022. CD200R1 Contributes to Successful Functional Reinnervation after a Sciatic Nerve Injury. In Cells, 11, . doi:10.3390/cells11111786. https://pubmed.ncbi.nlm.nih.gov/35681481/

3. Salek-Ardakani, Samira, Bell, Thomas, Jagger, Christopher P, Snelgrove, Robert J, Hussell, Tracy. 2019. CD200R1 regulates eosinophilia during pulmonary fungal infection in mice. In European journal of immunology, 49, 1380-1390. doi:10.1002/eji.201847861. https://pubmed.ncbi.nlm.nih.gov/31365119/

4. Zhao, Shou-Cai, Heng, Xu, Ya-Ping, Wang, Chu, Zhao-Hu, Xu, Yang. 2020. CD200-CD200R1 signaling pathway regulates neuroinflammation after stroke. In Brain and behavior, 10, e01882. doi:10.1002/brb3.1882. https://pubmed.ncbi.nlm.nih.gov/33067924/

5. Lin, Suzhen, Shu, Yimei, Shen, Ruinan, Xu, Wei, Ding, Jianqing. 2024. The regulation of NFKB1 on CD200R1 expression and their potential roles in Parkinson's disease. In Journal of neuroinflammation, 21, 229. doi:10.1186/s12974-024-03231-3. https://pubmed.ncbi.nlm.nih.gov/39294682/

6. Qian, Haitao, Gao, Fei, Wu, Xuyang, Chen, Xiaohui, Zheng, Xiaochun. 2023. Activation of the CD200/CD200R1 axis attenuates neuroinflammation and improves postoperative cognitive dysfunction via the PI3K/Akt/NF-κB signaling pathway in aged mice. In Inflammation research : official journal of the European Histamine Research Society ... [et al.], 72, 2127-2144. doi:10.1007/s00011-023-01804-1. https://pubmed.ncbi.nlm.nih.gov/37902837/

7. Linley, Holly, Jaigirdar, Shafqat, Mohamed, Karishma, Griffiths, Christopher E M, Saunders, Amy. . Reduced cutaneous CD200:CD200R1 signaling in psoriasis enhances neutrophil recruitment to skin. In Immunity, inflammation and disease, 10, e648. doi:10.1002/iid3.648. https://pubmed.ncbi.nlm.nih.gov/35759230/