Increased number of mature dendritic cells in Crohn's disease: evidence for a chemokine mediated retention mechanism
Increased number of mature dendritic cells in Crohn's disease: evidence for a chemokine mediated retention mechanism
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DOI：
10.1136/gut.2004.063008
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发表时间：
2006-02-01
期刊：
影响因子：
24.5
通讯作者：
Radzun, HJ
中科院分区：
文献类型：
--
作者：
Middel, P;Raddatz, D;Radzun, HJ
背景和目的：树突状细胞（DC）激活T细胞被认为在克罗恩病的诱导和维持中起关键作用。然而，关于DC的表型和成熟以及它们在克罗恩病中的募集机制的详细分析仍然缺乏。方法：采用免疫组织化学方法对不同的髓细胞和浆细胞样DC亚群进行表征。通过实时逆转录聚合酶链反应检测克罗恩病和正常对照中所谓的“淋巴样”趋化因子CCL19、CCL20和CCL21的表达。此外，CCL19、CCL20和CCL21及其受体CCR6（用于CCL20）和CCR7（用于CCL19和CCL21）的表达通过免疫组织化学表征，此外，它们的细胞定位通过双免疫荧光调查确定。结果：受克罗恩病影响的结肠组织的特征是成熟髓系DC形成簇的数量增加，T细胞增殖。随着它们的成熟，DC具有趋化因子受体CCR7。在克罗恩病中，我们观察到DC自身表达CCR7配体CCL19以及网状细胞和淋巴管表达CCL21的增加，从而导致成熟DC被困在炎症部位。结论：我们的研究结果表明，在克罗恩病中，淋巴样趋化因子的自分泌和旁分泌作用可能导致成熟DC的数量增加，而不是它们通常迁移到淋巴样器官，并导致肠壁内三级淋巴组织的发展，维持克罗恩病的自身免疫炎症。
Background and aims: Activation of T cells by dendritic cells ( DC) is thought to play a pivotal role in induction and maintenance of Crohn's disease. Detailed analyses however concerning the phenotype and maturation of DC as well as the mechanisms underlying their recruitment are still lacking for Crohn's disease.Methods: Different myeloid and plasmacytoid DC subsets were characterised by immunohistochemistry. Expression of the so-called "lymphoid'' chemokines CCL19, CCL20, and CCL21 was determined by real time reverse transcription-polymerase chain reaction in Crohn's disease and normal controls. Furthermore, expression of CCL19, CCL20, and CCL21 as well as their receptors CCR6 (for CCL20) and CCR7 (for CCL19 and CCL21) was characterised by immunohistochemistry and, in addition, their cellular localisation was determined by double immunofluorescence investigations.Results: Colonic tissue affected by Crohn's disease was characterised by an increased number of mature myeloid DC forming clusters with proliferating T cells. In keeping with their advanced maturation, DC possess the chemokine receptor CCR7. Increased expression of the CCR7 ligands CCL19 by DC themselves as well as CCL21 by reticular cells and lymphatic vessels was observed in Crohn's disease, thereby causing the matured DC to be trapped at the site of inflammation.Conclusion: Our results demonstrate that autocrine and paracrine actions of lymphoid chemokines in Crohn's disease may lead to increased numbers of mature DC away from their usual migration to lymphoid organs and result in the development of a tertiary lymphatic tissue within the bowel wall maintaining the autoimmune inflammation in Crohn's disease.