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(American Journal of Pathology. 2002;160:1445-1455.)
© 2002 American Society for Investigative Pathology

Regular Articles

Hepatic Expression of Secondary Lymphoid Chemokine (CCL21) Promotes the Development of Portal-Associated Lymphoid Tissue in Chronic Inflammatory Liver Disease

Allister J. Grant^*, Sarah Goddard^*, Jalal Ahmed-Choudhury^*, Gary Reynolds^*, David G. Jackson, Michael Briskin, Lijun Wu, Stefan G. Hübscher and David H. Adams^*

From the Liver Research Labs Centre for ImmuneRegulation^* and the Department ofPathology, University of Birmingham, QueenElizabeth Hospital, Birmingham, United Kingdom; the Medical ResearchCouncil Human Immunology Unit, Institute ofMolecular Medicine, John Radcliffe Hospital, Headington, Oxford, UnitedKingdom; and Millenium PharmaceuticalsIncorporated, Cambridge, Massachusetts

The chronic inflammatory liver disease primary sclerosing cholangitis (PSC) is associated with portal inflammation and the development of neolymphoid tissue in the liver. More than 70% of patients with PSC have a history of inflammatory bowel disease and we have previously reported that mucosal addressin cell adhesion molecule-1 is induced on dendritic cells and portal vascular endothelium in PSC. We now show that the lymph node-associated chemokine, CCL21 or secondary lymphoid chemokine, is also strongly up-regulated on CD34⁺ vascular endothelium in portal associated lymphoid tissue in PSC. In contrast, CCL21 is absent from LYVE-1⁺ lymphatic vessel endothelium. Intrahepatic lymphocytes in PSC include a population of CCR7⁺ T cells only half of which express CD45RA and which respond to CCL21 in migration assays. The expression of CCL21 in association with mucosal addressin cell adhesion molecule-1 in portal tracts in PSC may promote the recruitment and retention of CCR7⁺ mucosal lymphocytes leading to the establishment of chronic portal inflammation and the expanded portal-associated lymphoid tissue. This study provides further evidence for the existence of portal-associated lymphoid tissue and is the first evidence that ectopic CCL21 is associated with lymphoid neogenesis in human inflammatory disease.

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