| First Author | Ghazarian M | Year | 2017 |
| Journal | Sci Immunol | Volume | 2 |
| Issue | 10 | PubMed ID | 28567448 |
| Mgi Jnum | J:260885 | Mgi Id | MGI:6141628 |
| Doi | 10.1126/sciimmunol.aai7616 | Citation | Ghazarian M, et al. (2017) Type I Interferon Responses Drive Intrahepatic T cells to Promote Metabolic Syndrome. Sci Immunol 2(10) |
| abstractText | Obesity-related insulin resistance is driven by low-grade chronic inflammation of metabolic tissues. In the liver, non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and systemic glucose dysregulation. However, the immunological factors supporting these processes are poorly understood. We found that the liver accumulates pathogenic CD8+ T cell subsets which control hepatic insulin sensitivity and gluconeogenesis during diet-induced obesity in mice. In a cohort of human patients, CD8+ T cells represent a dominant intrahepatic immune cell population which links to glucose dysregulation. Accumulation and activation of these cells are largely supported by type I interferon (IFN-I) responses in the liver. Livers from obese mice upregulate critical interferon regulatory factors (IRFs), interferon stimulatory genes (ISGs), and IFNalpha protein, while IFNalphaR1(-/-) mice, or CD8-specific IFNalphaR1(-/-) chimeric mice are protected from disease. IFNalphaR1 inhibitors improve metabolic parameters in mice, while CD8+ T cells and IFN-I responses correlate with NAFLD activity in human patients. Thus, IFN-I responses represent a central immunological axis that governs intrahepatic T cell pathogenicity during metabolic disease. |
