Hepatic expression of secondary lymphoid chemokine (CCL21) promotes the development of portal-associated lymphoid tissue in chronic inflammatory liver disease

Am J Pathol. 2002 Apr;160(4):1445-55. doi: 10.1016/S0002-9440(10)62570-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Cells / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Chemokine CCL21
  • Chemokines, CC / physiology*
  • Cholangitis, Sclerosing / metabolism*
  • Cholangitis, Sclerosing / pathology*
  • Chronic Disease
  • Humans
  • Integrins / metabolism
  • Liver / metabolism*
  • Lymphocytes / metabolism
  • Lymphoid Tissue / pathology*
  • Portal System / pathology*
  • Receptors, CCR7
  • Receptors, Chemokine / blood
  • Receptors, Chemokine / metabolism
  • Reference Values
  • T-Lymphocytes / physiology


  • CCL21 protein, human
  • CCR7 protein, human
  • Chemokine CCL21
  • Chemokines, CC
  • Integrins
  • Receptors, CCR7
  • Receptors, Chemokine
  • integrin alpha4beta7