Lymphocyte recruitment to the liver in alcoholic liver disease

Haydon, Geoffrey; Lalor, Patricia F.; Hubscher, Stefan G.; Adams, David H.

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Volume 27, Issue 1 , Pages 29-36, May 2002

Lymphocyte recruitment to the liver in alcoholic liver disease☆

The Liver Research Laboratories, The University of Birmingham Institute of Clinical Science, MRC Centre for Immune Regulation, The Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TT, UK

Received 23 November 2001; received in revised form 22 January 2002; accepted 3 February 2002.

Abstract

The normal liver contains a large number of lymphocytes, which include not only specialized natural killer (NK) and NKT cells but also CD4 and CD8 T cells. Whereas some of these cells are terminally differentiated effector cells that are destined to die by apoptosis, many of them are not and include immunocompetent cells that traffic through the liver to provide continuing immune surveillance as well as epithelial-associated effector T cells. In alcoholic liver disease the number of lymphocytes in the liver increases and the type and distribution of these infiltrating cells will determine the nature of the inflammation. For instance, a predominance of parenchymal inflammation is a feature of alcoholic hepatitis, whereas a predominantly portal infiltrate is a feature of cirrhosis. In this article we discuss the molecular mechanisms that regulate the entry of lymphocytes to the inflamed liver in alcoholic hepatitis. Lymphocytes play a critical role in regulating the immune/inflammatory response to alcohol, and understanding how these cells are recruited to the liver has important implications for understanding the pathogenesis of alcoholic liver disease in which parenchymal infiltration is a critical determinant of disease progression. Aberrant recruitment and retention of lymphocytes in the liver may explain why some patients with alcoholic liver disease show progressive inflammatory damage whereas in others the disease takes a more indolent course. Similarly, leukocyte recruitment may present new therapeutic targets in which lymphocyte recruitment to the specific liver compartments can be inhibited, thereby minimizing tissue damage whilst leaving generalized lymphocyte recirculation intact. Potentially the most exciting potential is to modulate the nature of the lymphocyte subsets recruited to the liver, so that harmful cells are excluded and beneficial subsets are preferentially recruited.

Keywords: Alcoholic liver disease, Lymphocyte recruitment, Chemokines, Inflammation