Ceacam1, also known as carcinoembryonic antigen-related cell adhesion molecule 1, CC1, or CD66a, is a transmembrane glycoprotein. It is expressed on epithelial, endothelial, and immune cells and is involved in cell adhesion, immune regulation, and metabolic homeostasis. CEACAM1 participates in pathways related to T-cell inhibition, neutrophil activation, and insulin sensitivity [1,2,3,4]. It plays a significant role in maintaining epithelial polarity, liver tolerance, and mucosal immunity [4]. Gene knockout mouse models have been crucial in understanding its functions.

In gene knockout studies, Ceacam1-deficient T cells in a mouse adoptive transfer colitis model were hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, indicating Ceacam1's role in regulating T-cell-mediated tolerance [1]. Ablation of recipient-derived neutrophil Ceacam1-long isotype in a mouse orthotopic liver transplantation model aggravated hepatic ischemia-reperfusion injury by promoting neutrophil extracellular traps, suggesting its role in neutrophil-mediated innate immune-driven injury [3]. In mice, deletion or functional inactivation of Ceacam1 impairs insulin clearance, compromises metabolic homeostasis, and initiates the development of obesity, hepatic steatosis, fibrosis, and adipogenesis [4]. Loss of endothelial Ceacam1 in mice led to hepatic fibrosis, highlighting its role in preventing fibrogenesis [5].

In conclusion, Ceacam1 is essential for immune and metabolic regulation. Mouse gene knockout models have revealed its critical roles in autoimmunity, anti-tumor immunity, liver transplantation-related injury, and metabolic diseases such as non-alcoholic fatty liver disease and hepatic fibrosis. Understanding Ceacam1's functions provides insights into the pathogenesis of these diseases and potential therapeutic targets.

References:

1. Huang, Yu-Hwa, Zhu, Chen, Kondo, Yasuyuki, Kuchroo, Vijay K, Blumberg, Richard S. 2014. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. In Nature, 517, 386-90. doi:10.1038/nature13848. https://pubmed.ncbi.nlm.nih.gov/25363763/

2. Kim, Walter M, Huang, Yu-Hwa, Gandhi, Amit, Blumberg, Richard S. . CEACAM1 structure and function in immunity and its therapeutic implications. In Seminars in immunology, 42, 101296. doi:10.1016/j.smim.2019.101296. https://pubmed.ncbi.nlm.nih.gov/31604530/

3. Hirao, Hirofumi, Kojima, Hidenobu, Dery, Kenneth J, Kaldas, Fady M, Kupiec-Weglinski, Jerzy W. 2023. Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation. In The Journal of clinical investigation, 133, . doi:10.1172/JCI162940. https://pubmed.ncbi.nlm.nih.gov/36719377/

4. Horst, Andrea Kristina, Najjar, Sonia M, Wagener, Christoph, Tiegs, Gisa. 2018. CEACAM1 in Liver Injury, Metabolic and Immune Regulation. In International journal of molecular sciences, 19, . doi:10.3390/ijms19103110. https://pubmed.ncbi.nlm.nih.gov/30314283/

5. Muturi, Harrison T, Ghadieh, Hilda E, Abdolahipour, Raziyeh, Duarte, Sergio, Najjar, Sonia M. 2023. Loss of CEACAM1 in endothelial cells causes hepatic fibrosis. In Metabolism: clinical and experimental, 144, 155562. doi:10.1016/j.metabol.2023.155562. https://pubmed.ncbi.nlm.nih.gov/37088122/