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Tim-3 blockade promotes iNKT cell function to inhibit HBV replication.

Tim-3 blockade promotes iNKT cell function to inhibit HBV replication.
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Xu Y, Wang Z, Du X, Liu Y, Song X, Wang T, Tan S, Liang X, Gao L, Ma C,


Xu Y, Wang Z, Du X, Liu Y, Song X, Wang T, Tan S, Liang X, Gao L, Ma C, (click to view)

Xu Y, Wang Z, Du X, Liu Y, Song X, Wang T, Tan S, Liang X, Gao L, Ma C,

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Journal of cellular and molecular medicine 2018 03 30() doi 10.1111/jcmm.13600
Abstract

Increased expression of T cell immunoglobulin and mucin domain-3 (Tim-3) on invariant natural killer T (iNKT) cells is reported in chronic hepatitis B virus (HBV) infection. However, whether Tim-3 regulates iNKT cells in chronic HBV condition remains unclear. In this study, our results showed that the expression of Tim-3 was up-regulated on hepatic iNKT cells from HBV-transgenic (Tg) mice or iNKT cells stimulated with α-galactosylceramide (α-Galcer). Compared with Tim-3iNKT cells, Tim-3iNKT cells expressed more IFN-γ, IL-4 and CD107a, indicating a strong relationship between Tim-3 and iNKT cell activation. Constantly, treatment of Tim-3 blocking antibodies significantly enhanced the production of IFN-γ, TNF-α, IL-4 and CD107a in iNKT cells both in vivo and in vitro. This Tim-3mediated suppression of iNKT cells was further confirmed in Tim-3 knockout (KO) mice. Moreover, Tim-3 blockade promoted α-Galcer-triggered inhibition of HBV replication, displaying as the decreased HBV DNA and HBsAg level in serum, and down-regulated pgRNA expression in liver tissues. Collectively, our data, for the first time, demonstrated the potential role of Tim-3 blockade in promoting iNKT cell-mediated HBV inhibition. Therefore, combination of α-Galcer with Tim-3 blockade might be a promising approach in chronic hepatitis B therapy.

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