{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:43:58Z","timestamp":1787028238520,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R &amp; D Program of China","award":["2023YFD1300400"],"award-info":[{"award-number":["2023YFD1300400"]}]},{"name":"National Key R &amp; D Program of China","award":["2021YFD1300800"],"award-info":[{"award-number":["2021YFD1300800"]}]},{"name":"National Key R &amp; D Program of China","award":["32472857"],"award-info":[{"award-number":["32472857"]}]},{"name":"National Key R &amp; D Program of China","award":["32421005"],"award-info":[{"award-number":["32421005"]}]},{"name":"National Key R &amp; D Program of China","award":["32225046"],"award-info":[{"award-number":["32225046"]}]},{"name":"National Key R &amp; D Program of China","award":["32372846"],"award-info":[{"award-number":["32372846"]}]},{"name":"National Key R &amp; D Program of China","award":["32341051"],"award-info":[{"award-number":["32341051"]}]},{"name":"National Key R &amp; D Program of China","award":["2023CQBSHTB3098"],"award-info":[{"award-number":["2023CQBSHTB3098"]}]},{"name":"National Natural Science Foundation of China","award":["2023YFD1300400"],"award-info":[{"award-number":["2023YFD1300400"]}]},{"name":"National Natural Science Foundation of China","award":["2021YFD1300800"],"award-info":[{"award-number":["2021YFD1300800"]}]},{"name":"National Natural Science Foundation of China","award":["32472857"],"award-info":[{"award-number":["32472857"]}]},{"name":"National Natural Science Foundation of China","award":["32421005"],"award-info":[{"award-number":["32421005"]}]},{"name":"National Natural Science Foundation of China","award":["32225046"],"award-info":[{"award-number":["32225046"]}]},{"name":"National Natural Science Foundation of China","award":["32372846"],"award-info":[{"award-number":["32372846"]}]},{"name":"National Natural Science Foundation of China","award":["32341051"],"award-info":[{"award-number":["32341051"]}]},{"name":"National Natural Science Foundation of China","award":["2023CQBSHTB3098"],"award-info":[{"award-number":["2023CQBSHTB3098"]}]},{"name":"Chongqing Postdoctoral Special Funding","award":["2023YFD1300400"],"award-info":[{"award-number":["2023YFD1300400"]}]},{"name":"Chongqing Postdoctoral Special Funding","award":["2021YFD1300800"],"award-info":[{"award-number":["2021YFD1300800"]}]},{"name":"Chongqing Postdoctoral Special Funding","award":["32472857"],"award-info":[{"award-number":["32472857"]}]},{"name":"Chongqing Postdoctoral Special Funding","award":["32421005"],"award-info":[{"award-number":["32421005"]}]},{"name":"Chongqing Postdoctoral Special Funding","award":["32225046"],"award-info":[{"award-number":["32225046"]}]},{"name":"Chongqing Postdoctoral Special Funding","award":["32372846"],"award-info":[{"award-number":["32372846"]}]},{"name":"Chongqing Postdoctoral Special Funding","award":["32341051"],"award-info":[{"award-number":["32341051"]}]},{"name":"Chongqing Postdoctoral Special Funding","award":["2023CQBSHTB3098"],"award-info":[{"award-number":["2023CQBSHTB3098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: CD161, encoded by the KLRB1 gene, is an inhibitory receptor expresses on various immune cell and has gained attention in immune checkpoint research. In recent studies, KLRB1 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 KLRB1 involved in the liver for the prevention of liver diseases. Methods: We compared KO mice with wild-type controls by routine blood analysis and RNA-seq, and additionally performed H&amp;E staining and qPCR to validate the differentially expressed genes (DEGs). Results:KO mice had fewer lymphocytes compared to the wild-type mice. A transcriptomic analysis showed that Klrb1 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&amp;E staining reveals an inflammatory response around the central venous vessels in the liver tissue of the KO mice. Conclusions: We conclude that Klrb1 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 Klrb1 in hepatic health.<\/jats:p>","DOI":"10.3390\/genes15111444","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T06:05:41Z","timestamp":1731045941000},"page":"1444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Klrb1 Loss Promotes Chronic Hepatic Inflammation and Metabolic Dysregulation"],"prefix":"10.3390","volume":"15","author":[{"given":"Shuqi","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8611-7230","authenticated-orcid":false,"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pig Production, Chongqing Academy of Animal Science, Chongqing 400000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pig Production, Chongqing Academy of Animal Science, Chongqing 400000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9256-8856","authenticated-orcid":false,"given":"Yongju","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haohuan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhou","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0960-1529","authenticated-orcid":false,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 610000, China"},{"name":"Department of Pig Production, Chongqing Academy of Animal Science, Chongqing 400000, China"},{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7791","DOI":"10.4049\/jimmunol.175.12.7791","article-title":"Cutting Edge: Lectin-Like Transcript 1 Is a Ligand for the CD161 Receptor","volume":"175","author":"Aldemir","year":"2005","journal-title":"J. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7796","DOI":"10.4049\/jimmunol.175.12.7796","article-title":"Cutting Edge: Lectin-Like Transcript-1 Is a Ligand for the Inhibitory Human NKR-P1A Receptor","volume":"175","author":"Rosen","year":"2005","journal-title":"J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s002510050679","article-title":"Cloning of a New Lectin-like Receptor Expressed on Human NK Cells","volume":"50","author":"Boles","year":"1999","journal-title":"Immunogenetics"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Braud, V.M., Meghraoui-Kheddar, A., Elaldi, R., Petti, L., Germain, C., and Anju\u00e8re, F. (2022). LLT1-CD161 Interaction in Cancer: Promises and Challenges. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.847576"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/d41573-021-00038-2","article-title":"T Cell Atlas Reveals Route to Glioma Immunotherapy","volume":"20","author":"Crunkhorn","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/hep.26115","article-title":"Natural Killer Cells in Liver Disease","volume":"57","author":"Tian","year":"2013","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1206737","DOI":"10.1155\/2018\/1206737","article-title":"Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy","volume":"2018","author":"Liu","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kirkham, C.L., and Carlyle, J.R. (2014). Complexity and Diversity of the NKR-P1: Clr (Klrb1: Clec2) Recognition Systems. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00214"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jameson, G., and Robinson, M.W. (2021). Insights into Human Intrahepatic NK Cell Function From Single Cell RNA Sequencing Datasets. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.649311"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"E37688","DOI":"10.1097\/MD.0000000000037688","article-title":"A Comprehensive Analysis of the KLRB1 Expression and Its Clinical Implication in Testicular Germ Cell Tumors: A Review","volume":"103","author":"Li","year":"2024","journal-title":"Medicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e008694","DOI":"10.1136\/jitc-2023-008694","article-title":"Poor Clinical Outcomes and Immunoevasive Contexture in CD161+CD8+ T Cells Barren Human Pancreatic Cancer","volume":"12","author":"Chen","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e008667","DOI":"10.1136\/jitc-2023-008667","article-title":"Single-Cell Analysis Reveals Cellular and Molecular Factors Counteracting HPV-Positive Oropharyngeal Cancer Immunotherapy Outcomes","volume":"12","author":"Cha","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2371575","DOI":"10.1080\/2162402X.2024.2371575","article-title":"CD161+CD127+CD8+ T Cell Subsets Can Predict the Efficacy of Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer with Diabetes Mellitus","volume":"13","author":"Qu","year":"2024","journal-title":"OncoImmunology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"199457","DOI":"10.1016\/j.virusres.2024.199457","article-title":"New Insights into Potential Biomarkers and Their Roles in Biological Processes Associated with Hepatitis C-Related Liver Cirrhosis by Hepatic RNA-Seq-Based Transcriptome Profiling","volume":"349","author":"Shahmahmoodi","year":"2024","journal-title":"Virus Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fang, S., and Zhou, Y. (2024). Deciphering the Role of KLRB1: A Novel Prognostic Indicator in Hepatocellular Carcinoma. BMC Gastroenterol., 24.","DOI":"10.1186\/s12876-024-03299-4"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.cell.2021.01.022","article-title":"Inhibitory CD161 Receptor Identified in Glioma-Infiltrating T Cells by Single-Cell Analysis","volume":"184","author":"Mathewson","year":"2021","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1002\/2211-5463.12724","article-title":"Whole Transcriptome Analysis of Chemically Induced Hepatocellular Carcinoma Using RNA-Sequencing Analysis","volume":"9","author":"Sun","year":"2019","journal-title":"FEBS Open Bio"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"82621","DOI":"10.18632\/oncotarget.19734","article-title":"Lingguizhugan Decoction Improves Non-Alcoholic Fatty Liver Disease by Altering Insulin Resistance and Lipid Metabolism Related Genes: A Whole Trancriptome Study by RNA-Seq","volume":"8","author":"Zhu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_19","first-page":"2579","article-title":"Visualizing Data Using T-SNE","volume":"9","author":"Hinton","year":"2008","journal-title":"J. Mach. Learn. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.it.2017.01.004","article-title":"Regulation of Inflammation- and Infection-Driven Hematopoiesis","volume":"38","author":"Boettcher","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Johnson, C.B., Zhang, J., and Lucas, D. (2020). The Role of the Bone Marrow Microenvironment in the Response to Infection. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.585402"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1161\/01.CIR.0000017140.26466.F5","article-title":"Platelet-Monocyte Aggregates: Bridging Thrombosis and Inflammation","volume":"105","author":"Freedman","year":"2002","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s00018-018-2976-8","article-title":"The Inflammatory Function of Human IgA","volume":"76","author":"Hansen","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.immuni.2011.05.007","article-title":"Review Regulation of the Antimicrobial Response by NLR Proteins","volume":"34","author":"Elinav","year":"2011","journal-title":"Immunity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.4049\/jimmunol.1601048","article-title":"Innate Immune Cell Recovery Is Positively Regulated by NLRP12 during Emergency Hematopoiesis","volume":"198","author":"Linz","year":"2017","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jaci.2016.02.046","article-title":"Current Concepts in Chronic Inflammatory Diseases: Interactions between Microbes, Cellular Metabolism, and Inflammation","volume":"138","author":"Garn","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"136584","DOI":"10.1155\/2013\/136584","article-title":"Mechanisms of Chronic State of Inflammation as Mediators That Link Obese Adipose Tissue and Metabolic Syndrome","volume":"2013","author":"Fuentes","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1126\/science.1178331","article-title":"Development of Monocytes, Macrophages, and Dendritic Cells","volume":"327","author":"Geissmann","year":"2010","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Goto, K., Morimoto, M., Osaki, M., Tanio, A., Izutsu, R., Fujiwara, Y., and Okada, F. (2022). The Impact of AMIGO2 on Prognosis and Hepatic Metastasis in Gastric Cancer Patients. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09339-0"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bauernfeind, A.L., and Babbitt, C.C. (2017). The Predictive Nature of Transcript Expression Levels on Protein Expression in Adult Human Brain. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3674-x"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5910575","DOI":"10.1155\/2022\/5910575","article-title":"CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types","volume":"2022","author":"Jiang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jss.2015.03.070","article-title":"Kif20a Inhibition Reduces Migration and Invasion of Pancreatic Cancer Cells","volume":"197","author":"Stangel","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gao, W., Lu, J., Yang, Z., Li, E., Cao, Y., and Xie, L. (2024). Mitotic Functions and Characters of KIF11 in Cancers. Biomolecules, 14.","DOI":"10.3390\/biom14040386"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.3892\/ijo.2014.2559","article-title":"Increased CDC20 Expression Is Associated with Development and Progression of Hepatocellular Carcinoma","volume":"45","author":"Li","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.3892\/ijo.2020.5141","article-title":"NUF2 as an Anticancer Therapeutic Target and Prognostic Factor in Breast Cancer","volume":"57","author":"Lv","year":"2020","journal-title":"Int. J. Oncol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/11\/1444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:28:41Z","timestamp":1760113721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/11\/1444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["genes15111444"],"URL":"https:\/\/doi.org\/10.3390\/genes15111444","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]}}}