Grant Allister J, Goddard Sarah, Ahmed-Choudhury Jalal, Reynolds Gary, Jackson David G, Briskin Michael, Wu Lijun, Hübscher Stefan G, Adams David H
Liver Research Labs Centre for Immune Regulation and the Department of Pathology, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.
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.
慢性炎症性肝病原发性硬化性胆管炎（PSC）与门静脉炎症及肝脏新淋巴组织的形成有关。超过70%的PSC患者有炎症性肠病病史，我们之前报道过黏膜地址素细胞黏附分子-1在PSC的树突状细胞和门静脉血管内皮细胞上被诱导表达。我们现在发现，淋巴结相关趋化因子CCL21或二级淋巴趋化因子，在PSC门静脉相关淋巴组织中的CD34(+)血管内皮细胞上也强烈上调。相比之下，LYVE-1(+)淋巴管内皮细胞中不存在CCL21。PSC肝内淋巴细胞包括一群CCR7(+) T细胞，其中只有一半表达CD45RA，并且在迁移试验中对CCL21有反应。PSC门静脉区域中CCL21与黏膜地址素细胞黏附分子-1共同表达，可能促进CCR7(+)黏膜淋巴细胞的募集和滞留，导致慢性门静脉炎症的形成以及门静脉相关淋巴组织的扩大。本研究为门静脉相关淋巴组织的存在提供了进一步证据，并且是异位CCL21与人类炎症性疾病中淋巴新生相关的首个证据。
