Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.11887
Peer-review started: January 29, 2015
First decision: April 13, 2015
Revised: April 27, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: November 14, 2015
The liver, which is a metabolic organ, plays a pivotal role in tolerance induction. Hepatic stellate cells (HpSCs), which are unique non-parenchymal cells, exert potent immunoregulatory activity during cotransplantation with allogeneic islets effectively protecting the islet allografts from rejection. Multiple mechanisms participate in the immune tolerance induced by HpSCs, including the marked expansion of myeloid-derived suppressor cells (MDSCs), attenuation of effector T cell functions and augmentation of regulatory T cells. HpSC conditioned MDSC-based immunotherapy has been conducted in mice with autoimmune disease and the results show that this technique may be promising. This article demonstrates how HpSCs orchestrate both innate immunity and adaptive immunity to build a negative network that leads to immune tolerance.
Core tip: The liver is an immune privileged organ that contains cells exhibiting powerful immune regulatory activity. Hepatic stellate cells (HpSCs) possess weak antigen-presenting ability and function as immunological bystander cells in the regulation of the immune response by the way of induction of effector T cell apoptosis and the generation of myeloid-derived suppressor cells and regulatory T cells. The combination of these mechanisms indicates that HpSCs are a potent immunoregulatory entity capable of modulating immune responses in the liver. HpSCs can orchestrate both innate immunity and adaptive immunity to build a negative immune network that leads to immune tolerance. Further understanding of hepatic immune tolerance will provide the basis for developing new immunotherapies that target transplant rejection, chronic viral infection and cancer.