title: Hepatic expression of secondary lymphoid chemokine (CCL21) promotes the development of portal-associated lymphoid tissue in chronic inflammatory liver disease.
abstract: 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.
authors.affiliation: Liver Research Labs Centre for Immune Regulation and the Department of Pathology, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Allister J
authors.initials: AJ
authors.lastname: Grant
authors.forename: Sarah
authors.initials: S
authors.lastname: Goddard
authors.forename: Jalal
authors.initials: J
authors.lastname: Ahmed-Choudhury
authors.forename: Gary
authors.initials: G
authors.lastname: Reynolds
authors.forename: David G
authors.initials: DG
authors.lastname: Jackson
authors.forename: Michael
authors.initials: M
authors.lastname: Briskin
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Hübscher
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
mesh_terms: D001773:Blood Cells / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology*; D015209:Cholangitis, Sclerosing / Q000378:metabolism* / Q000473:pathology*; D002908:Chronic Disease; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008221:Lymphoid Tissue / Q000473:pathology*; D011168:Portal System / Q000473:pathology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000097:blood / Q000378:metabolism; D012016:Reference Values; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016023:Integrins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C071777:integrin alpha4beta7