Cd300lf, also known as myeloid-associated Ig-like receptor V (MAIR-V), is an inhibitory immunoreceptor. It belongs to the CD300 family and plays crucial roles in multiple biological processes. It binds to ligands like ceramide and phosphatidylserine, and is involved in regulating immune cell activation and viral infection. Genetic models, such as gene knockout mouse models, are valuable for studying its functions [1,3,4,5].

In Cd300lf-deficient mice, increased glial cell proliferation, more extensive neuronal loss, and worsened neurological function were observed post-traumatic brain injury (TBI), indicating its role in reducing neuroinflammation and promoting neurological recovery, likely via inhibiting the STING signaling pathway [1]. A Cd300lf conditional knockout (CD300lfF/F) mouse model revealed that CD300lf expression on intestinal epithelial cells, especially tuft cells, is essential for transmission of the persistent murine norovirus (MNoV) strain CR6 in vivo, while myelomonocytic cells are a major target for the non-persistent MNoV strain CW3 [2]. Ablation of Cd300lf in a ligature-induced periodontitis model increased the number of osteoclasts and exacerbated bone damage, suggesting its role in inhibiting osteoclast differentiation and alveolar bone loss in periodontitis [3].

In conclusion, Cd300lf is involved in neuroinflammation regulation after TBI, norovirus cell tropism, and osteoclast-related bone homeostasis. The Cd300lf KO/CKO mouse models have significantly contributed to understanding its functions in these disease-related areas, providing potential therapeutic targets for TBI, norovirus-related diseases, and periodontitis.

References:

1. Lu, Zhichao, Liu, Zongheng, Wang, Chenxing, Yang, Yang, Gong, Peipei. . CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway. In CNS neuroscience & therapeutics, 30, e14824. doi:10.1111/cns.14824. https://pubmed.ncbi.nlm.nih.gov/38965803/

2. Graziano, Vincent R, Alfajaro, Mia Madel, Schmitz, Cameron O, Orchard, Robert C, Wilen, Craig B. 2021. CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus. In Journal of virology, 95, . doi:10.1128/JVI.01652-20. https://pubmed.ncbi.nlm.nih.gov/33177207/

3. Hu, Qiannan, Yang, Lisa, Shan, Zhongyan, Yang, Le, Wang, Xi. 2022. The interaction of CD300lf and ceramide reduces the development of periodontitis by inhibiting osteoclast differentiation. In Journal of clinical periodontology, 50, 183-199. doi:10.1111/jcpe.13724. https://pubmed.ncbi.nlm.nih.gov/36089906/

4. Lee, Hanbin, Nakahashi-Oda, Chigusa, Lyu, Wenxin, Shibuya, Kazuko, Shibuya, Akira. 2025. Inhibitory immunoreceptors CD300a and CD300lf cooperate to regulate mast cell activation. In Journal of immunology (Baltimore, Md. : 1950), , . doi:10.1093/jimmun/vkae030. https://pubmed.ncbi.nlm.nih.gov/40073110/

5. Can, Ismail, Tahara-Hanaoka, Satoko, Hitomi, Kaori, Shibuya, Kazuko, Shibuya, Akira. . Caspase-independent cell death by CD300LF (MAIR-V), an inhibitory immunoglobulin-like receptor on myeloid cells. In Journal of immunology (Baltimore, Md. : 1950), 180, 207-13. doi:. https://pubmed.ncbi.nlm.nih.gov/18097021/