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


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 ?-galactosylceramide (?-Galcer). Compared with Tim-3- iNKT cells, Tim-3+ iNKT cells expressed more IFN-?, 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-?, TNF-?, IL-4 and CD107a in iNKT cells both in vivo and in vitro. This Tim-3- mediated suppression of iNKT cells was further confirmed in Tim-3 knockout (KO) mice. Moreover, Tim-3 blockade promoted ?-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 ?-Galcer with Tim-3 blockade might be a promising approach in chronic hepatitis B therapy.

SUBMITTER: Xu Y 

PROVIDER: S-EPMC5980221 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Xu Yong Y   Wang Zehua Z   Du Xianhong X   Liu Yuan Y   Song Xiaojia X   Wang Tixiao T   Tan Siyu S   Liang Xiaohong X   Gao Lifen L   Ma Chunhong C  

Journal of cellular and molecular medicine 20180330 6


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-3<sup>-</sup> iNKT cells, T  ...[more]

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