Klrb1 Loss Promotes Chronic Hepatic Inflammation and Metabolic Dysregulation

<b>Background/Objectives:</b> CD161, encoded by the <i>KLRB1</i> gene, is an inhibitory receptor expresses on various immune cell and has gained attention in immune checkpoint research. In recent studies, <i>KLRB1</i> has been found to be one of the potential markers of liver diseases such as cirrhosis. Therefore, it will be important to understand what process <i>KLRB1</i> involved in the liver for the prevention of liver diseases. <b>Methods:</b> We compared <i>KO</i> mice with wild-type controls by routine blood analysis and RNA-seq, and additionally performed H&E staining and qPCR to validate the differentially expressed genes (DEGs). <b>Results:</b><i>KO</i> mice had fewer lymphocytes compared to the wild-type mice. A transcriptomic analysis showed that <i>Klrb1</i> loss causes the upregulation of immune-related genes and pathways like NOD-like receptor and p53 signaling, while causing the downregulation of lipid metabolism-related genes. A protein interaction analysis indicated a potential cancer risk under chronic inflammation. Histological examination with H&E staining reveals an inflammatory response around the central venous vessels in the liver tissue of the <i>KO</i> mice. <b>Conclusions</b>: We conclude that <i>Klrb1</i> knockout disrupts the immune and metabolic functions in the liver, which may possibly lead to chronic inflammation and malignancy risks. These findings highlight the role of <i>Klrb1</i> in hepatic health.