The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics
The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics
复制标题
鞘氨醇 1-磷酸受体 1 通过抑制外周组织 T 淋巴细胞进入传入淋巴管而导致组织滞留
DOI：
10.1038/ni1534
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发表时间：
2008-01-01
影响因子：
30.5
通讯作者：
Bromberg, Jonathan S.
中科院分区：
文献类型：
--
作者：
Ledgerwood, Levi G.;Lal, Girdhari;Bromberg, Jonathan S.
尽管人们对 T 细胞从血液迁移到淋巴结的了解很多，但对于调节 T 细胞通过传入淋巴管从组织迁移到淋巴结的机制知之甚少。在这里，我们研究了体内 T 细胞从非淋巴组织进入传入淋巴的过程，并开发了一个实验模型来在体外重现这一过程。 1-磷酸鞘氨醇受体 I 的激动作用抑制组织 T 细胞在稳态和炎症条件下进入传入淋巴管，并导致淋巴管而非血管基底表面的极化 T 细胞的停滞，这至少部分是通过整合素 LFA-1 与其配体 ICAM-1 以及整合素 VLA-4 与其配体 VCAM-1 的相互作用介导的 内皮细胞。因此，发炎的外周组织中存在的 1-磷酸鞘氨醇增加可能会诱导 T 细胞滞留并抑制 T 细胞流出。
Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an experimental model to recapitulate this process in vitro. Agonism of sphingosine 1-phosphate receptor I inhibited the entry of tissue T cells into afferent lymphatics in homeostatic and inflammatory conditions and caused the arrest, mediated at least partially by interactions of the integrin LFA-1 with its ligand ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at the basal surface of lymphatic but not blood vessel endothelium. Thus, the increased sphingosine 1-phosphate present in inflamed peripheral tissues may induce T cell retention and suppress T cell egress.