Alpha-lactose reverses liver injury via blockade of Tim-3-mediated CD8 apoptosis in sepsis

Zhengping Wei; Pingfei Li; Yao Yao; Hai Deng; Shengwu Yi; Cong Zhang; Han Wu; Xiuxiu Xie; Minghui Xia; Ran He; Xiang-Ping Yang; Zhao-Hui Tang

doi:10.1016/j.clim.2018.04.010

Alpha-lactose reverses liver injury via blockade of Tim-3-mediated CD8 apoptosis in sepsis

Clin Immunol. 2018 Jul:192:78-84. doi: 10.1016/j.clim.2018.04.010. Epub 2018 Apr 22.

Authors

Zhengping Wei¹, Pingfei Li¹, Yao Yao², Hai Deng², Shengwu Yi², Cong Zhang², Han Wu², Xiuxiu Xie¹, Minghui Xia¹, Ran He¹, Xiang-Ping Yang¹, Zhao-Hui Tang³

Affiliations

¹ Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
² Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
³ Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: tangzh@tjh.tjmu.edu.cn.

PMID: 29689313
DOI: 10.1016/j.clim.2018.04.010

Abstract

In sepsis, the liver plays a crucial role in regulating immune responses and is also a target organ for immune-related injury. Despite the critical function of CD8⁺ T cells against opportunistic viral infections, the CD8 immune response in the liver during sepsis remains elusive. Here we found that Tim-3 is highly up-regulated in liver CD8⁺ T cells in a mouse cecal ligation and puncture model and in peripheral blood CD8⁺ T cells of human patients with sepsis. The expression of Tim-3 in liver CD8⁺ T cells displayed a bi-phasic pattern and deletion of Tim-3 led to reduction of CD8⁺ T cell apoptosis. Administration of α-lactose, a molecule with a similar structure to galactin-9, reduced Tim-3 expression and liver injury in sepsis. Our results demonstrate that targeting Tim-3 to boost CD8⁺ T cell immune response may offer an improved outcome in patients with sepsis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Apoptosis / genetics
Apoptosis / immunology
CD8-Positive T-Lymphocytes / drug effects*
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism
Cells, Cultured
Cytokines / genetics
Cytokines / immunology
Cytokines / metabolism
Gene Expression / drug effects
Gene Expression / immunology
Hepatitis / genetics
Hepatitis / immunology
Hepatitis / prevention & control
Hepatitis A Virus Cellular Receptor 2 / antagonists & inhibitors*
Hepatitis A Virus Cellular Receptor 2 / genetics
Hepatitis A Virus Cellular Receptor 2 / immunology
Humans
Lactose / administration & dosage
Lactose / pharmacology*
Leukocytes, Mononuclear / drug effects
Leukocytes, Mononuclear / immunology
Leukocytes, Mononuclear / metabolism
Liver / drug effects*
Liver / metabolism
Liver / pathology
Mice, Inbred C57BL
Sepsis / genetics
Sepsis / immunology*
Sepsis / metabolism

Substances

Cytokines
Havcr2 protein, mouse
Hepatitis A Virus Cellular Receptor 2
Lactose