Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2015; 21(42): 11887-11892
Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.11887
Hepatic immune tolerance induced by hepatic stellate cells
Ching-Chuan Hsieh, Chien-Hui Hung, Lina Lu, Shiguang Qian
Ching-Chuan Hsieh, Department of Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi 613, Taiwan
Ching-Chuan Hsieh, Chien-Hui Hung, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan
Lina Lu, Shiguang Qian, Department of Immunology, Lerner Research Institute, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, United States
Lina Lu, Shiguang Qian, Department of General Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, United States
Author contributions: Hsieh CC, Lu L and Qian S contributed to the conception, design, acquisition and interpretation of the data; Hung CH contributed to the revision of manuscript; all authors revised the article and approved the final version.
Supported by National Science Council, No. NSC 101-2314-B-182A-040-MY2 and No. CMRPG6A0523.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ching-Chuan Hsieh, MD, Department of Surgery, Chang Gung Memorial Hospital at Chiayi, 6 Sec. West Chia-Pu Road, Pu-Zi City, Chiayi 613, Taiwan. jeffrey570404@gmail.com
Telephone: +886-5-3621000 Fax: +886-5-3623002
Received: January 28, 2015
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
Processing time: 286 Days and 22.7 Hours
Abstract

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.

Keywords: Hepatic stellate cells; Myeloid-derived suppressor cells; Hepatic tolerance; Immunotherapy

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.