Differential Activation of Unconventional T Cells, Including iNKT Cells, in Alcohol-Related Liver Disease
| Autor: | Marrero, Idania, Maricic, Igor, Morgan, Timothy R, Stolz, Andrew A, Schnabl, Bernd, Liu, Zhang-Xu, Tsukamoto, Hidekazu, Kumar, Vipin |
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| Rok vydání: | 2020 |
| Předmět: |
Male
T-Lymphocytes Chronic Liver Disease and Cirrhosis Clinical Sciences CD8-Positive T-Lymphocytes Chronic Alcoholic Inbred C57BL Lymphocyte Activation IFN gamma Mucosal-Associated Invariant T Cells Oral and gastrointestinal Cell Line Hepatitis Mice Alcohol Use and Health Substance Misuse Animals Humans 2.1 Biological and endogenous factors Psychology Lymphocyte Count Aetiology iG ASH Model Nutrition Ethanol Liver Diseases Liver Disease Neurosciences Substance Abuse CD8 Middle Aged Alcoholic Alcoholism Good Health and Well Being Liver Cytokines Natural Killer T-Cells Alcohol-Related Liver Disease Digestive Diseases NK Cell Lectin-Like Receptor Subfamily B IFNγ |
| Zdroj: | Alcoholism, clinical and experimental research, vol 44, iss 5 |
| Popis: | BackgroundLiver is enriched in several innate-like unconventional T cells, but their role in alcohol-related liver disease (ALD) is not fully understood. Studies in several acute alcohol feeding models but not in chronic alcoholic steatohepatitis (ASH) model have shown that invariant natural killer T (iNKT) cells play a pathogenic role in ALD. Here, we investigated the activation of iNKT cells in an intragastric (iG) infusion model of chronic ASH as well as the frequency and cytokine phenotype of 3 different unconventional T cells: iNKT, mucosal-associated invariant T (MAIT), and CD8+ CD161hi Vα7.2- cells in peripheral blood of ALD patients.MethodsHepatic iNKT cells were investigated using the iG model of chronic ASH that combines feeding of high-cholesterol/high-fat diet (HCFD) with intragastric feeding of ethanol diet (HCFD+iG Alc). Human iNKT, MAIT, and CD8+ CD161hi Vα7.2- cells were examined by flow cytometry in peripheral blood of patients with severe alcoholic hepatitis (SAH) and chronic alcoholics (ChA) and compared with healthy controls.ResultsIn the iG model of chronic ASH, IFNγ+ iNKT cells accumulate in their livers compared with pair-fed control mice and activated hepatic iNKT cells show high expression of Fas and FasL. Notably, IFNγ+ iNKT cells are also significantly increased in peripheral blood of ChA patients compared with SAH patients. MAIT cells are significantly reduced in all ALD patients, but CD8+ CD161hi Vα7.2- cells are increased in SAH patients. Although MAIT and CD8+ CD161hi Vα7.2- cells displayed a similar cytokine production profile, the production of IFNγ and TNFα is significantly increased in SAH patients, while significant IL-17A production is found in ChA patients.ConclusionsWe found that the 3 unconventional T cells are activated in ALD patients showing interesting differences in their frequency and cytokine production profile between SAH and ChA patients. In the iG murine model of chronic ASH, iNKT cells are also activated secreting proinflammatory cytokines suggesting their involvement in liver disease. |
| Databáze: | OpenAIRE |
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