Lilrb4a, also known as Leukocyte immunoglobulin-like receptor B4a, is an immunosuppressive regulatory receptor. It plays a role in multiple biological processes and is involved in pathways such as NF-κB signaling and MAPK signaling. Its biological importance spans across various disease-related processes including cardiovascular, bone, and cancer-related events [1-3]. Genetic models, especially gene knockout mouse models, have been crucial in studying its functions.

In an isoproterenol (ISO)-induced mouse model, Lilrb4a knockout and overexpression mice were used. The results showed that ISO led to cardiac hypertrophy, fibrosis, inflammation, electrical remodeling, and ventricular arrhythmias. Lilrb4a alleviated these effects by inhibiting NF-κB and MAPK signaling activation mediated by transforming growth factor kinase 1. This indicates that Lilrb4a can protect against ISO-induced arrhythmogenic remodeling and cardiac dysfunction [1]. In mice expressing constitutively active TGF-β receptor type I, silencing Lilrb4 increased the number of osteoclasts and osteoclast marker genes, suggesting its role in bone turnover [2]. Also, in a mouse model of circadian rhythm disruption-induced aggressive basal tumorigenesis, enhanced LILRB4a expression was found to disrupt mammary gland morphology, increase tumor burden and lung metastasis, and induce an immunosuppressive tumor microenvironment. Targeted immunotherapy against LILRB4a reduced these effects [3].

In conclusion, Lilrb4a is a key player in various biological functions. Through model-based research, especially using KO mouse models, its role in cardiovascular diseases like preventing cardiac dysfunction and arrhythmogenic remodeling, in bone turnover by influencing osteoclast numbers, and in cancer-related processes such as tumor-associated immunosuppression and metastasis has been revealed. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Fu, Hui, Kong, Bin, Shuai, Wei, Huang, He, Huang, Congxin. 2024. Leukocyte Ig-like receptor B4 (Lilrb4a) alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation. In Heart rhythm, 21, 1998-2009. doi:10.1016/j.hrthm.2024.04.062. https://pubmed.ncbi.nlm.nih.gov/38636927/

2. Myint, Ohnmar, Sakunrangsit, Nithidol, Pholtaisong, Jatuphol, Greenblatt, Matthew B, Lotinun, Sutada. 2024. Differential Gene Expression Involved in Bone Turnover of Mice Expressing Constitutively Active TGFβ Receptor Type I. In International journal of molecular sciences, 25, . doi:10.3390/ijms25115829. https://pubmed.ncbi.nlm.nih.gov/38892016/

3. Ogunlusi, Olajumoke, Sarkar, Mrinmoy, Chakrabarti, Arhit, Jones, Jeff, Sarkar, Tapasree Roy. 2024. Disruption of Circadian Clock Induces Abnormal Mammary Morphology and Aggressive Basal Tumorigenesis by Enhancing LILRB4 Signaling. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.03.19.585534. https://pubmed.ncbi.nlm.nih.gov/38562905/