Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease
Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease
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DOI：
10.1136/jcp.2004.024828
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发表时间：
2005-10-01
影响因子：
3.4
通讯作者：
Arakawa, T
中科院分区：
文献类型：
--
作者：
Kawashima, D;Oshitani, N;Arakawa, T
背景：一种显性辅助性T型1 （Th1）免疫应答被认为与克罗恩病（CD）有关。SLC/CCL21和ELC/CCL19是调节T细胞归巢和促进T循环和树突状细胞（DC）相互作用的趋化因子，有助于控制抗原特异性T细胞反应。目的：探讨Th1应答和SLC、ELC在CD发病机制中的作用。方法：对手术切除的肠和肠系膜淋巴结（MLNs）进行对照和乳糜泻合并溃疡性结肠炎（UC）患者的调查。免疫组织化学检测CD3、CD83、HECA452、VEGFR3、SLC、ELC和CCR7的表达。采用实时RT-PCR定量CCR7 mRNA。结果：肠标本中几乎检测不到ELC。淋巴滤泡、淋巴聚集体小静脉和淋巴管零星可见SLC。在MLNs中，SLC在高内皮小静脉（HEVs）、淋巴管和间质dc中高度表达，主要在T细胞区表达。ELC在成熟的dc中高表达。在CD中，SLC阳性的hev和ELC阳性的成熟dc （T细胞区域的重要组成部分）明显更多。与UC相比，SLC、ELC和CCR7 mRNA在CD MLNs中显著升高。CD MLNs中SLC和ELC的表达增加，主要发生在hev、成熟dc和淋巴管中，诱导T细胞增生。T细胞区CCR7 mRNA表达升高。结论：在增生性T细胞区，SLC阳性hev /淋巴管、ELC阳性成熟dc和CCR7阳性T细胞的相互作用促进了显性Th1免疫应答。在CD中，记忆T细胞和成熟的dc可能是MLN的宿主。
Background: A dominant T helper type 1 (Th1) immune response is thought to be involved in Crohn's disease ( CD). SLC/CCL21 and ELC/CCL19, chemokines that regulate T cell homing and promote recirculating T and dendritic cell ( DC) interactions, help control antigen specific T cell responses.Aims: To investigate the Th1 response and SLC and ELC in CD pathogenesis.Methods: Surgically resected intestine and mesenteric lymph nodes (MLNs) from controls and patients with CD and ulcerative colitis (UC) were investigated. CD3, CD83, HECA452, VEGFR3, SLC, ELC, and CCR7 expression was studied immunohistochemically. CCR7 mRNA was quantified using real time RT-PCR.Results: ELC was almost undetectable in intestinal samples. SLC was found sporadically in lymphoid follicles, lymphoid aggregate venules, and lymphatic vessels. In MLNs, SLC was highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal DCs, predominantly in T cell areas. ELC was highly expressed in mature DCs. There were significantly more SLC positive HEVs and ELC positive mature DCs, important components of T cell areas, in CD. SLC, ELC, and CCR7 mRNA was significantly higher in CD MLNs compared with UC. CD MLNs had increased expression of SLC and ELC, mainly in HEVs, mature DCs, and lymphatic vessels, inducing T cell hyperplasia. CCR7 mRNA was increased in T cell areas.Conclusion: The dominant Th1 immune response is facilitated by interaction of SLC positive HEVs/ lymphatic vessels, ELC positive mature DCs, and CCR7 positive T cells in hyperplastic T cell areas. In CD, memory T cells and mature DCs may home to MLN.