Cd200r1, short for CD200 receptor 1, is a membrane glycoprotein. It is mainly found on microglia and is crucial for maintaining their quiescence. The CD200:CD200R1 inhibitory signaling pathway plays a prominent role in limiting inflammation in a wide range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules such as tumor necrosis factor, interferons, and inducible nitric oxide synthase in response to selected stimuli [1].

In a sciatic nerve crush injury model in C57Bl/6 mice, blockade of CD200R1 significantly reduced the acute entrance of neutrophils and monocytes from blood after nerve injury, and impaired the spontaneous functional recovery, indicating that CD200R1 has a role in mounting a successful acute inflammatory reaction after injury and contributes to effective functional recovery [2]. In a mouse model of Cryptococcus neoformans infection, CD200R1 blockade enhanced eosinophilia, while CD200R1 agonism reduced lung eosinophilia, suggesting that agonists of CD200R1 may be beneficial for eosinophilic pathologies [3]. In a stroke mouse model, stimulation of CD200R1 by CD200Fc promoted the anti-inflammatory response and alleviated ischemic injury [4]. In NFKB1 knockout mice, exacerbated microglia activation and dopaminergic neuron loss were observed after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment, indicating that reduced NFKB1, a direct regulator of CD200R1, plays a critical role in CD200R1 dysregulation and subsequent microglia overactivation in Parkinson's disease [5]. In mouse models of psoriasis, CD200R1 was shown to limit psoriasis-like inflammation by enhancing acanthosis, CCL20 production and neutrophil recruitment, and in CD200R1 -deficient mice, psoriasis models were less severe due to reduced IL-17 production [6,8]. In aged mice with postoperative cognitive dysfunction (POCD) model, CD200Fc attenuated neuroinflammation and synaptic deficits and reversed cognitive impairment, while CD200R1 Ab administration exerted the opposite effects [7].

In conclusion, CD200R1 plays a vital role in regulating inflammation, immune responses, and functional recovery in various biological processes and disease conditions, such as nerve injury, fungal infection, stroke, Parkinson's disease, psoriasis, and POCD. Gene knockout or blockade models of CD200R1 in mice have provided valuable insights into its functions, highlighting its potential as a therapeutic target for these diseases.