In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines
In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines
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DOI：
10.1189/jlb.0603250
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发表时间：
2004-03-01
影响因子：
5.5
通讯作者：
Ishii, H
中科院分区：
文献类型：
--
作者：
Kobayashi, H;Miura, S;Ishii, H
树突状细胞（DC）从肠连续转运至肠系膜淋巴结（MLN）。本研究的目的是确定DCs通过肠淋巴的迁移动力学，并研究影响其体内迁移的调节因素。从肠系膜淋巴结切除大鼠的脾或胸导管淋巴液中获得DC。将DC荧光标记并注射到盲肠附近的小肠浆膜下，并确定它们向MLN的迁移模式。从肠淋巴中分离的DC表达细胞间粘附分子-1（ICAM-1）、CD 11b/c、CD 80/86和主要组织相容性复合物II类，但保持其吞噬乳胶颗粒的能力，表明存在未成熟的DC。分离的DC在MLN中以时间依赖性方式积累，在48 h时达到最大积累。细胞因子诱导的淋巴DC成熟没有引起细胞数量的变化，但加速了它们向MLN的转运，在24 h时达到最大值。脾脏DCs表现出中等水平的成熟和类似于成熟DCs的迁移模式。ICAM-1或CD 11b/c的抑制不影响DC迁移。成熟DC向MLN的迁移通过用CCL 21使CCR 7脱敏而特异性阻断。与此相反，新鲜分离的淋巴DCs不趋化CCL 21，但其迁移到MLN主要是抑制CCR 6与CCL 20的脱敏。DC的迁移能力与其成熟程度密切相关，不同趋化因子/趋化因子受体的使用可能是DC通过肠淋巴迁移动力学的主要调节因子。
Dendritic cells (DCs) are continuously transported from the intestine to mesenteric lymph nodes (MLNs). The objective of this study was to determine the migration kinetics of DCs via intestinal lymph and to investigate regulatory factors affecting their migration in vivo. DCs were obtained from spleen or thoracic duct lymph of mesenteric lymphadenectomized rats. The DCs were fluorescently labeled and injected into the subserosa of the small intestine near the cecum, and their migration patterns into MLNs were determined. Isolated DCs from intestinal lymph express intercellular adhesion molecule-1 (ICAM-1), CD11b/c, CD80/86, and major histocompatibility complex class II but maintain their ability to phagocytize latex particles, suggesting the presence of immature DCs. The isolated DCs accumulated in MLNs in a time-dependent manner with maximal accumulation at 48 h. Cytokine-induced maturation of lymph DCs did not cause a change in cell number but accelerated their transport into MLNs with a maximum at 24 h. Splenic DCs showed an intermediate level of maturation and a migration pattern similar to mature DCs. Inhibition of ICAM-1 or CD11b/c did not affect DC migration. Migration of mature DCs to MLNs was specifically blocked by desensitization of CCR7 with CCL21. In contrast, freshly isolated lymph DCs were not chemotactic for CCL21, but their migration to MLNs was mainly inhibited by desensitization of CCR6 with CCL20. The migratory ability of DCs correlates well with their degree of maturation, and different chemokine/chemokine receptor use may be the main regulator of DC migration kinetics through intestinal lymph.