Cd300lf, an inhibitory immunoglobulin-like receptor, has diverse functions. It's involved in regulating cell activation, as it contains motifs in its cytoplasmic tail suggesting regulation of myeloid cell activation [7]. It also serves as a receptor, with murine Cd300lf identified as the receptor for murine norovirus (MNoV), playing a role in viral cell tropism and pathogenesis [2,4,5,6].

Cd300lf-deficient mice showed increased glial cell proliferation, more neuronal loss, and worsened neurological function post-traumatic brain injury (TBI), indicating its role in reducing neuroinflammation and promoting neurological recovery by inhibiting the STING pathway [1]. In norovirus research, Cd300lf conditional knockout (CD300lfF/F) mice demonstrated that CD300lf expression on intestinal epithelial cells, especially tuft cells, is essential for transmission of the persistent MNoV strain CR6 in vivo. Deletion of Cd300lf in myelomonocytic cells partially reduced the viral load of the non-persistent MNoVCW3 strain in lymphoid and intestinal tissues [2]. In periodontitis, ablation of Cd300lf in a ligature-induced periodontitis model increased osteoclasts and exacerbated bone damage, showing its role in inhibiting osteoclast differentiation and alveolar bone loss through interaction with ceramide [3].

In summary, Cd300lf is crucial in multiple biological processes and disease conditions. Cd300lf KO/CKO mouse models have revealed its importance in TBI, norovirus infection, and periodontitis. These models provide valuable insights into its functions, such as regulating neuroinflammation, viral cell tropism, and osteoclast-mediated bone loss, which could potentially lead to new therapeutic strategies for related diseases.

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. Graziano, Vincent R, Walker, Forrest C, Kennedy, Elizabeth A, Baldridge, Megan T, Wilen, Craig B. 2020. CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus. In PLoS pathogens, 16, e1008242. doi:10.1371/journal.ppat.1008242. https://pubmed.ncbi.nlm.nih.gov/32251490/

5. Furlong, Kevin, Biering, Scott B, Choi, Jayoung, Randall, Glenn, Hwang, Seungmin. 2020. CD300LF Polymorphisms of Inbred Mouse Strains Confer Resistance to Murine Norovirus Infection in a Cell Type-Dependent Manner. In Journal of virology, 94, . doi:10.1128/JVI.00837-20. https://pubmed.ncbi.nlm.nih.gov/32581099/

6. Haga, Kei, Fujimoto, Akira, Takai-Todaka, Reiko, Nakanishi, Akira, Katayama, Kazuhiko. 2016. Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells. In Proceedings of the National Academy of Sciences of the United States of America, 113, E6248-E6255. doi:. https://pubmed.ncbi.nlm.nih.gov/27681626/

7. 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/