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World J Gastrointest Pathophysiol. May 15, 2014; 5(2): 107-113
Published online May 15, 2014. doi: 10.4291/wjgp.v5.i2.107
Role of gamma-delta T cells in liver inflammation and fibrosis
Linda Hammerich, Frank Tacke
Linda Hammerich, Frank Tacke, Department of Medicine III, University Hospital Aachen, 52074 Aachen, Germany
Author contributions: Hammerich L and Tacke F contributed equally to this paper.
Supported by The German Research Foundation, No. DFG Ta434/2-1 and SFB/TRR57; by the Interdisciplinary Center for Clinical Research (IZKF) Aachen
Correspondence to: Frank Tacke, MD, PhD, Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
Telephone: +49-241-8035848 Fax: +49-241-8082455
Received: December 17, 2013
Revised: February 4, 2014
Accepted: March 13, 2014
Published online: May 15, 2014

Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis, especially in chronic viral infections and autoimmune hepatitis. However, the role of unconventional gamma-delta (γδ) T cells in liver diseases is less clear. In the past two decades, accumulating evidence revealed that γδ T cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans. More recent studies demonstrated that the functional effect of γδ T cells on liver disease progression depends on the subsets involved, which can be identified by the expression of distinct T cell receptor chains and of specific cytokines. Fascinatingly, γδ T cells may have protective as well as pathogenic functions in liver diseases. Interferon γ-producing γδ T cells, for example, induce apoptosis in hepatocytes but also in hepatic tumor cells; while interleukin-17-expressing γδ T cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells. However, the results obtained in human liver disease as well as murine models are not fully conclusive at present, and the effects of γδ T cells on the outcome of liver disease might vary dependent on etiology and stage of disease. Further definitions of the γδ T cell subsets involved in acute and chronic liver inflammation, as well as their effector cytokines might uncover whether interference with γδ T cells could be a useful target for the treatment of liver disease.

Keywords: Liver fibrosis, Liver cirrhosis, Interleukin-17, Gamma/delta T cells, Cytokines

Core tip: The liver is particularly enriched in unconventional T cells expressing the gamma-delta T cell receptor and the functional role of these gamma-delta (γδ) T cells in liver diseases is being intensively investigated at present. γδ T cells accumulate in inflamed liver and their function appears highly dependent on the distinct subsets. In principle, γδ T cells can be protective as well as pathogenic in the context of liver inflammation. This review summarizes the current knowledge of γδ T cell effector functions and the cytokines produced by these cells in human liver diseases and murine experimental models of acute and chronic liver injury.