Natural killer T cells play a necessary role in modulating of immune-mediated liver injury by gut microbiota

Abstract

Gut microbiota are implicated in many liver diseases. Concanavalin A (ConA)-induced hepatitis is a well-characterized murine model of fulminant immunological hepatic injury. Oral administration of pathogenic bacteria or gentamycin to the mice before ConA injection, liver injury and lymphocyte distribution in liver and intestine were assessed. Our data show that administration of pathogenic bacteria exacerbated the liver damage. There was more downregulation of activation-induced natural killer T (NKT) cells in the liver of pathogenic bacteria-treated ConA groups. Also, there was a negative correlation between the numbers of hepatic NKT cells and liver injury in our experiments. Moreover, intestinal dendritic cells (DCs) were increased in pathogenic bacteria–treated ConA groups. The activation of DCs in Peyer's patches and the liver was similar to the intestine. However, depletion of gut gram-negative bacteria alleviated ConA-induced liver injury, through suppressed hepatic NKT cells activation and DCs homing in liver and intestine. In vitro experiments revealed that DCs promoted NKT cell cytotoxicity against hepatocyte following stimulation with pathogenic bacteria. Our study suggests that increased intestinal pathogenic bacteria facilitate immune-mediated liver injury, which may be due to the activation of NKT cells that mediated by intestinal bacterial antigens activated DCs.

Cellular Innate Immunity: An Old Game with New Players

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Influence of autologous dendritic cells on cytokine-induced killer cell proliferation, cell phenotype and antitumor activity in vitro

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“…DCs, known to be the most powerful APCs, play a significant role in immune response regulation, induce primary immune responses, and potentiate the effector functions of previously primed T lymphocytes (17)(18)(19). Usually, tumor patients have low immune function, which leads to tumor cells escaping autoimmune response.…”

The effects of hemocyanin on T cells cultured in�vitro

“…1) + is the characteristic marker of T cells (20). The CD3 + CD4 + phenotype is characteristic of T helper cells, which secret anti-tumor agents for cytotoxic T lymphocytes (21). T cells with the CD3 + CD8 + phenotype are critical factors in the immune response to viral infection and cancer (22).…”