Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis
Chisom Ifeoma Adaeze Okwor,
Jun Seok Oh,
Angela Marie Crawley,
Curtis Lindsey Cooper,
Seung-Hwan Lee
Affiliations
Chisom Ifeoma Adaeze Okwor
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada
Jun Seok Oh
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada
Angela Marie Crawley
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa K1Y 4E9, Canada; Division of Infectious Diseases, Ottawa Hospital-General Campus, Ottawa K1H 8L6, Canada; The University of Ottawa Centre for Infection, Immunity, and Inflammation, Ottawa K1H 8M5, Canada; Department of Biology, Carleton University, Ottawa K1S 5B6, Canada
Curtis Lindsey Cooper
Division of Infectious Diseases, Ottawa Hospital-General Campus, Ottawa K1H 8L6, Canada; The University of Ottawa Centre for Infection, Immunity, and Inflammation, Ottawa K1H 8M5, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa K1Y 4E9, Canada; Department of Medicine, University of Ottawa, Ottawa K1H 8M5, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa K1G 5Z3, Canada
Seung-Hwan Lee
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada; The University of Ottawa Centre for Infection, Immunity, and Inflammation, Ottawa K1H 8M5, Canada; Corresponding author
Summary: Chronic HCV can result in advanced liver disease, including cirrhosis. Patients with advanced fibrosis experience poor clinical outcomes and increased risk for hepatocellular carcinoma (HCC). These outcomes are, in part, a consequence of immune dysfunction. Increased inhibitory receptor and Galectin-9 (GAL-9) expression is a possible mechanism promoting lymphocyte dysfunction. In this study, we measured the expression of inhibitory receptors and GAL-9 on T/NK cells of patients with chronic HCV with no to moderate fibrosis (F0-F2) and advanced fibrosis (F3-F4). To analyze their co-expression, we employed t-SNE analysis. Notably, we found that F3-F4 patients had higher frequencies of >3 inhibitory receptor co-expression on NK cells. Moreover, F3-F4 patients manifest a higher frequency of NK cells co-expressing TIGIT and TIM-3, and CD4/NK cells co-expressing LAG-3 and GAL-9. In conclusion, we identified phenotypes of immune dysregulation that could explain the increased susceptibility to infection and HCC in patients with chronic HCV with advanced fibrosis.
