Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A-deficient mice.
Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A-deficient mice.
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DOI：
10.1172/jci21231
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发表时间：
2004-09
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通讯作者：
M. Cera;A. Del Prete;A. Vecchi;M. Corada;I. Martìn‐padura;T. Motoike;Paolo Tonetti;G. Bazzoni;W. Vermi;F. Gentili;S. Bernasconi;Thomas N. Sato;A. Mantovani;E. Dejana
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文献类型：
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作者：
M. Cera;A. Del Prete;A. Vecchi;M. Corada;I. Martìn‐padura;T. Motoike;Paolo Tonetti;G. Bazzoni;W. Vermi;F. Gentili;S. Bernasconi;Thomas N. Sato;A. Mantovani;E. Dejana
连接粘附分子-A (JAM-A) 是一种在内皮连接处和白细胞中表达的跨膜粘附蛋白。在目前的工作中，我们发现 DC 也表达 JAM-A。为了评估这一观察结果的生物学相关性，制备了 Jam-A(-/-) 小鼠并研究了 DC 的体外和体内功能行为。在体外，Jam-A(-/-) DCs表现出随机运动和跨淋巴管内皮细胞迁移能力的选择性增加。在体内，Jam-A(-/-) 小鼠表现出增强的 DC 向淋巴结迁移，而在内皮限制性蛋白质缺陷的小鼠中未观察到这一点。此外，DC 向淋巴结迁移的增加与接触性超敏反应 (CHS) 的增强有关。过继转移实验表明，JAM-A 缺陷的 DC 会在 Jam-A(+/+) 小鼠中引起 CHS 增加，进一步支持 DC 特异性效应的概念。因此，我们在此发现了 JAM-A 在控制 DC 运动、运输至淋巴结和激活特异性免疫方面的一种新颖的、非冗余的作用。
Junctional adhesion molecule-A (JAM-A) is a transmembrane adhesive protein expressed at endothelial junctions and in leukocytes. In the present work, we found that DCs also express JAM-A. To evaluate the biological relevance of this observation, Jam-A(-/-) mice were generated and the functional behavior of DCs in vitro and in vivo was studied. In vitro, Jam-A(-/-) DCs showed a selective increase in random motility and in the capacity to transmigrate across lymphatic endothelial cells. In vivo, Jam-A(-/-) mice showed enhanced DC migration to lymph nodes, which was not observed in mice with endothelium-restricted deficiency of the protein. Furthermore, increased DC migration to lymph nodes was associated with enhanced contact hypersensitivity (CHS). Adoptive transfer experiments showed that JAM-A-deficient DCs elicited increased CHS in Jam-A(+/+) mice, further supporting the concept of a DC-specific effect. Thus, we identified here a novel, non-redundant role of JAM-A in controlling DC motility, trafficking to lymph nodes, and activation of specific immunity.