Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2018; 24(18): 1962-1977
Published online May 14, 2018. doi: 10.3748/wjg.v24.i18.1962
Ambiguous roles of innate lymphoid cells in chronic development of liver diseases
Yue Shen, Jing Li, Si-Qi Wang, Wei Jiang
Yue Shen, Jing Li, Si-Qi Wang, Wei Jiang, Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Jing Li, Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai 200000, China
Author contributions: Jiang W conceived this topic and organized the manuscript; Shen Y wrote the first draft of the manuscript and drew the figures; Li J and Wang SQ contributed to manuscript revision; all authors have read and approved the submitted version and are accountable for all aspects of the work.
Supported by National Nature Science Foundation of China, No. 81670541; and National Science and Technology Major Project, No. 2013ZX10002004 and No. 2017ZX10203202.
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential 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:
Correspondence to: Wei Jiang, MD, PhD, Academic Research, Chief Doctor, Professor, Department of Gastroenterology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai 200032, China.
Telephone: +86-21-64041990-2424 Fax: +86-21-64432583
Received: March 29, 2018
Peer-review started: March 30, 2018
First decision: April 19, 2018
Revised: April 25, 2018
Accepted: May 6, 2018
Article in press: May 6, 2018
Published online: May 14, 2018

Innate lymphoid cells (ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs (including natural killer (NK) cells and ILC1s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs (ILC2s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin (IL)-5 and IL-13; and, group 3 ILCs (including lymphoid tissue-like cells and ILC3s) are dependent on RORγt and can produce IL-22 and IL-17. Collaborative with adaptive immunity, ILCs are highly reactive innate effectors that promptly orchestrate immunity, inflammation and tissue repair. Dysregulation of ILCs might result in inflammatory disorders. Evidence regarding the function of intrahepatic ILCs is emerging from longitudinal studies of inflammatory liver diseases wherein they exert both physiological and pathological functions, including immune homeostasis, defenses and surveillance. Their overall effect on the liver depends on the balance of their proinflammatory and antiinflammatory populations, specific microenvironment and stages of immune responses. Here, we review the current data about ILCs in chronic liver disease progression, to reveal their roles in different stages as well as to discuss their therapeutic potency as intervention targets.

Keywords: Innate lymphoid cells, Chronic liver disease, Hepatitis, Liver fibrosis, Liver cancer

Core tip: Innate lymphoid cells (ILCs), mirroring both the phenotypes and functions of T cells, have been defined as a distinct arm of innate immunity. There has been a marked increase in the studies investigating the dysregulation of ILCs in chronic liver pathologies. This manuscript presents a comprehensive overview of the state of ILCs, including the fundamental concepts as well as summarizing their ambiguous roles in the progression of the chronic liver hepatitis, fibrosis and carcinoma. It also provides an insight into the current research gaps and indicates the therapeutic potency and development direction of future research of ILCs.