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  • Opinion
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Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease

Nature Reviews Immunology volume 6, pages 244–251 (2006)Cite this article

Abstract

Active inflammatory bowel disease (IBD) is often associated with simultaneous inflammation in the skin, eyes and joints. Inflammatory disease in the liver can also occur in patients with IBD but seems to be independent of inflammation in the bowel. In this Opinion article, we propose that the hepatic complications of IBD are mediated by long-lived mucosal T cells that are recruited to the liver in response to aberrantly expressed endothelial-cell adhesion molecules and chemokines that are normally restricted to the gut. Similar mechanisms might explain why certain diseases are associated with site-specific tissue distributions and might point to new therapeutic strategies that are based on modulating tissue-specific lymphocyte homing.

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Figure 1: Three-dimensional structure of a liver lobule.
Figure 2: Adhesion molecules and recruitment of lymphocytes to the liver.
Figure 3: Homing of mucosal lymphocytes in the pathogenesis of hepatic disease that is associated with inflammatory bowel disease.

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Acknowledgements

We would like to thank A. Grant, A. Miles, S. Curbishley and P. Lalor, who have contributed to work discussed in this article, and M. Briskin, S. Jalkanen and M. Salmi, who have contributed intellectually to the development of the ideas. B.E. is funded by Fellowships from Core and the Medical Research Council, UK, and the work has also been supported by funding from the European Commission, the Wellcome Trust and a research grant from Pfizer Inc. We would also like to thank C. Buckley, A. Rickinson and M. Salmon for critical review of the manuscript.

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  1. the Liver Research Laboratories, MRC Centre for Immune Regulation, 5th Floor, Institute for Biomedical Research, Medical School, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK

    David H. Adams & Bertus Eksteen

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  1. David H. Adams
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Correspondence to David H. Adams.

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A family of peptides (endothelin 1, endothelin 2 and endothelin 3) that are produced in various tissues. They function as modulators of vasomotor tone, cell proliferation and hormone production.

Porta hepatis

A transverse fissure on the abdominal surface of the liver, where the portal vein, hepatic artery and hepatic ducts enter the liver. Also known as the hilum.

Primary sclerosing cholangitis

A persistent chronic inflammatory disease that is focused in the intrahepatic and extrahepatic bile ducts and is often associated with inflammatory bowel disease.

Sieve plates

A cluster of small holes (fenestrae) in a liver sinusoidal endothelial cell, which is thought to facilitate the diffusion of molecules between the hepatic sinusoid and the underlying space of Disse, which is where solutes can interact with hepatocytes.

Space of Disse

Located between the hepatocytes and the sinusoid, the space of Disse contains hepatic stellate cells (myofibroblasts) and a network of reticular fibres that hold the hepatocytes together. Microvilli that extend from the hepatocytes increase the surface area exposed in the space of Disse.

Thromboxanes

Arachidonic-acid metabolites that are produced by the action of thromboxane synthetase on prostaglandin cyclic endoperoxides. They cause platelet aggregation, vasoconstriction and have pro-inflammatory properties.

Weibel–Palade bodies

(WPBs). Rod-shaped secretory granules that are found in endothelial cells. Exocytosis of WPBs in response to pro-inflammatory stimuli delivers the adhesive protein von Willebrand factor and the leukocyte adhesion molecule platelet selectin to the endothelial-cell surface, where they have important roles in vascular haemostasis and inflammation.

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Adams, D., Eksteen, B. Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol 6, 244–251 (2006). https://doi.org/10.1038/nri1784

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