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 | Allister J Grant, Sarah Goddard, Jalal Ahmed-Choudhury, Gary Reynolds, David G Jackson, Michael Briskin, Lijun Wu, Stefan G Hübscher, David H Adams |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 160
Issue 4
Pg. 1445-55
(Apr 2002)
ISSN: 0002-9440 [Print] United States |
PMID | 11943728
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- CCL21 protein, human
- CCR7 protein, human
- Chemokine CCL21
- Chemokines, CC
- Integrins
- Receptors, CCR7
- Receptors, Chemokine
- integrin alpha4beta7
|
Topics |
- Blood Cells
(physiology)
- Cell Movement
(physiology)
- Cells, Cultured
- Chemokine CCL21
- Chemokines, CC
(physiology)
- Cholangitis, Sclerosing
(metabolism, pathology)
- Chronic Disease
- Humans
- Integrins
(metabolism)
- Liver
(metabolism)
- Lymphocytes
(metabolism)
- Lymphoid Tissue
(pathology)
- Portal System
(pathology)
- Receptors, CCR7
- Receptors, Chemokine
(blood, metabolism)
- Reference Values
- T-Lymphocytes
(physiology)
|