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• W2921423889 abstract "Infiltrating CD4 and CD8 T cells have been shown to worsen inflammatory liver damage in non-alcoholic steatohepatitis (NASH). Inhibitory T cell receptors such as the programmed cell death protein 1 (PD1) and the natural killer cell receptor 2B4 regulate the activity of CD4 and CD8 T cells and therefore play an important role in immune tolerance required in the liver. In this study, we investigated the expression profile of inhibitory T cell receptors on CD4 and CD8 T cells in a mouse model of NASH. Male B57BL/6J mice were fed a Western diet for 24 weeks. The expression levels of inhibitory receptors on the surface of intrahepatic and peripheral T cells were measured and correlated with markers of activation (CD107a, CD69, and CD44), metabolic disorder (serum triglycerides, serum cholesterol, γ-glutamyl transferase, hepatic triglycerides), inflammation (serum alanine aminotransferase and aspartate aminotransferase) and hepatic fibrosis (collagen 1A1, α-smooth muscle actin, hydroxyproline). Under Western diet, PD1 is exclusively upregulated on intrahepatic and peripheral CD8+ T cells, whereas the expression level on CD4 T cells is unaffected. In contrast, 2B4 is upregulated liver-specifically on both CD4 and CD8 T cells and unchanged on peripheral T cells. Upregulation of PD1 on CD8 T cells is restricted to CD8 effector memory T cells and correlates with lower levels of degranulation. Similarly, the inhibitory function of PD1 on intrahepatic CD4 T cells is shown by a lower CD69 and CD44 expression on PD1-positive CD4 T cells. In murine steatohepatitis, the upregulation of PD1 on CD8 T cells and 2B4 on CD4 and CD8 T cells potentially limits T cell-mediated liver damage. Therefore, these inhibitory T cell receptors could serve as promising targets of immune-modulatory NASH therapy." @default.
• W2921423889 created "2019-03-22" @default.
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• W2921423889 date "2019-03-13" @default.
• W2921423889 modified "2023-10-10" @default.
• W2921423889 title "The Inhibitory T Cell Receptors PD1 and 2B4 Are Differentially Regulated on CD4 and CD8 T Cells in a Mouse Model of Non-alcoholic Steatohepatitis" @default.
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• W2921423889 doi "https://doi.org/10.3389/fphar.2019.00244" @default.
• W2921423889 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6436071" @default.
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