AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation.
AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation.
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DOI：
10.1038/ncomms10182
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发表时间：
2015-12-18
影响因子：
16.6
通讯作者：
Mayadas TN
中科院分区：
文献类型：
--
作者：
Herter JM;Grabie N;Cullere X;Azcutia V;Rosetti F;Bennett P;Herter-Sprie GS;Elyaman W;Luscinskas FW;Lichtman AH;Mayadas TN
驱动T细胞归巢到淋巴结和迁移到组织的机制已被很好地描述，但对影响T细胞从组织中迁移的因素知之甚少。在这里，我们产生了T细胞特异性缺失支架蛋白a激酶锚定蛋白9 （AKAP9）的小鼠，并使用炎症疾病模型证明AKAP9对于T细胞的启动和迁移到组织和淋巴结是必不可少的，但对于T细胞在组织中的保留是必需的。AKAP9缺乏导致T细胞向引流淋巴结的输出增加，这与组织中受损的T细胞再激活和器官损伤的保护有关。缺乏akap9的T细胞表现出tcr回细胞表面的微管依赖性循环减少，这主要影响非经典抗原提呈细胞的抗原依赖性活化。因此，依赖akap9的TCR运输驱动有效的T细胞再激活，并延长它们在炎症部位的保留，这与疾病发病机制有关。a激酶锚定蛋白9 （AKAP9）是一种结合信号蛋白并调节微管的支架蛋白。在这里，作者表明，在炎症期间，T细胞中的AKAP9是它们在炎症部位的再激活和保留所必需的，并且它的缺失可以保护它们免受炎症诱导的器官损伤。
The mechanisms driving T cell homing to lymph nodes and migration to tissue are well described but little is known about factors that affect T cell egress from tissues. Here, we generate mice with a T cell-specific deletion of the scaffold protein A kinase anchoring protein 9 (AKAP9) and use models of inflammatory disease to demonstrate that AKAP9 is dispensable for T cell priming and migration into tissues and lymph nodes, but is required for T cell retention in tissues. AKAP9 deficiency results in increased T cell egress to draining lymph nodes, which is associated with impaired T cell re-activation in tissues and protection from organ damage. AKAP9-deficient T cells exhibit reduced microtubule-dependent recycling of TCRs back to the cell surface and this affects antigen-dependent activation, primarily by non-classical antigen-presenting cells. Thus, AKAP9-dependent TCR trafficking drives efficient T cell re-activation and extends their retention at sites of inflammation with implications for disease pathogenesis. A-kinase anchoring protein 9 (AKAP9) is a scaffold protein that binds signalling proteins and regulates microtubules. Here the authors show that during inflammation AKAP9 in T cells is required for their reactivation and retention at the inflammation site and that its deletion protects from inflammation-induced organ damage.