Maturing dendritic cells depend on RAGE for in vivo homing to lymph nodes
Maturing dendritic cells depend on RAGE for in vivo homing to lymph nodes
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DOI：
10.4049/jimmunol.180.4.2270
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发表时间：
2008-02-15
影响因子：
4.4
通讯作者：
Del Maschiot, Alessandro
中科院分区：
文献类型：
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作者：
Manfredi, Angelo A.;Capobianco, Annalisa;Del Maschiot, Alessandro
从外周组织动员树突状细胞（DC）对于建立T细胞依赖性免疫应答或耐受是至关重要的，因为DC与初始T细胞的物理相互作用发生在淋巴结的T细胞区域。DC自分泌/旁分泌高迁移率族蛋白1（HMGB 1）核蛋白控制DC-T细胞相互作用的结果，影响初始T细胞的启动/Th 1极化。我们在此提供证据表明，晚期糖基化终产物受体（HMGB 1受体）是细胞表面分子IG超家族的多配体成员，在DC归巢至淋巴结中发挥非冗余作用。我们使用磁共振和免疫组织化学的非侵入性成像来追踪皮下注射后的DC。在野生型（+/+）或BALB/c（-/-）小鼠的足垫中注射。成熟的DCs在两种情况下都有效地表达CD 4 + T细胞。相比之下，CD 4（-/-）DC不能到达+/+和-/-小鼠的引流腘淋巴结，表明CD 4的完整性是DC动员所必需的。因此，HMGB 1-β通路是DC成熟和功能的检查点，也是靶向治疗的候选者。
The mobilization of dendritic cells (DCs) from peripheral tissues is critical for the establishment of T cell-dependent immune responses or tolerance, because the physical interaction of DCs with naive T cells takes place in the T cell areas of lymph nodes. The autocrine/paracrine release of the high mobility group box 1 (HMGB1) nuclear protein by DCs controls the outcome of the DC-T cell interaction, influencing the priming/Th1 polarization of naive T cells. We herein present evidence that the receptor for advanced glycation end products (RAGE), a multiligand member of the Ig superfamily of cell-surface molecules that acts as a receptor for HMGB1, plays a nonredundant role in DC homing to lymph nodes. We used noninvasive imaging by magnetic resonance and immunohistochemistry to track DCs after s.c. injection in the footpad of wild-type(+/+) or RAGE(-/-) mice. Maturing DCs expressing RAGE effectively migrated in both conditions. In contrast, RAGE(-/-) DCs failed to reach the draining popliteal lymph nodes of +/+ and -/- mice, indicating that the integrity of RAGE is required for DC mobilization. Thus the HMGB1-RAGE pathway is a checkpoint in DC maturation and function and a candidate for targeted therapies.