CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes
CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes
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DOI：
10.4049/jimmunol.180.9.6288
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Thompson, Linda F.
中科院分区：
文献类型：
--
作者：
Takedachi, Masahide;Qu, Dongfeng;Thompson, Linda F.
炎症刺激后，淋巴细胞向引流淋巴结的迁移显着增加，以促进初始 T 细胞与负载 Ag 的树突状细胞的相遇。在这项研究中，我们表明 CD73（ecto-5'-核苷酸酶）在调节这一过程中发挥着重要作用。 CD73 从 AMP 产生腺苷，并在高内皮微静脉 (HEV) 和淋巴细胞亚群上表达。 U73(-/-) 小鼠在稳态下具有正常大小的淋巴器官，但与野生型小鼠相比，LPS 给药 24 小时后，引流淋巴结增大 1.5 倍，L-选择素依赖性淋巴细胞通过 REV 从血液迁移的速率增加 2.5 倍。野生型小鼠的cd73(+/+)和cd73(-/-)淋巴细胞向淋巴结的迁移率是相等的，表明HEN上的CD73调节淋巴细胞向引流淋巴结的迁移。 A21 受体可能是 CD73 生成的腺苷的靶标，因为它是在 HEV 样细胞系 KOP2.16 上表达的唯一腺苷受体，并且它被 TNF-α 上调。此外，通过选择性 A(2B) 受体激动剂 BAY 60-6583 预处理，CD73(-/-) 小鼠引流淋巴结中淋巴细胞迁移的增加在很大程度上恢复正常。限制淋巴细胞跨 HEN 迁移的腺苷受体信号传导可能是控制炎症反应程度的重要机制。
After an inflammatory stimulus, lymphocyte migration into draining lymph nodes increases dramatically to facilitate the encounter of naive T cells with Ag-loaded dendritic cells. In this study, we show that CD73 (ecto-5'-nucleotidase) plays an important role in regulating this process. CD73 produces adenosine from AMP and is expressed on high endothelial venules (HEV) and subsets of lymphocytes. U73(-/-) mice have normal sized lymphoid organs in the steady state, but similar to 1.5-fold larger draining lymph nodes and 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through REV compared with wild-type mice 24 h after LPS administration. Migration rates of cd73(+/+) and cd73(-/-) lymphocytes into lymph nodes of wild-type mice are equal, suggesting that it is CD73 on HEN that regulates lymphocyte migration into draining lymph nodes. The A2, receptor is a likely target of CD73-generated adenosine, because it is the only adenosine receptor expressed on the HEV-like cell line KOP2.16 and it is up-regulated by TNF-alpha. Furthermore, increased lymphocyte migration into draining lymph nodes of cd73(-/-) mice is largely normalized by pretreatment with the selective A(2B) receptor agonist BAY 60-6583. Adenosine receptor signaling to restrict lymphocyte migration across HEN may be an important mechanism to control the magnitude of an inflammatory response.