Hepatic expression of secondary lymphoid chemokine (CCL21) promotes the development of portal-associated lymphoid tissue in chronic inflammatory liver disease.
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.
Grant
Allister J
AJ
Liver Research Labs Centre for Immune Regulation and the Department of Pathology, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Goddard
Sarah
S
Ahmed-Choudhury
Jalal
J
Reynolds
Gary
G
Jackson
David G
DG
Briskin
Michael
M
Wu
Lijun
L
Hübscher
Stefan G
SG
Adams
David H
DH
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
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