The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system
The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system
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DOI：
10.4049/jimmunol.165.9.5069
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发表时间：
2000-11-01
影响因子：
4.4
通讯作者：
Targan, SR
中科院分区：
文献类型：
--
作者：
Papadakis, KA;Prehn, J;Targan, SR
趋化因子在白细胞在炎症部位的迁移中发挥重要作用，一些组成型表达的趋化因子可能指导淋巴细胞在淋巴器官和外周组织内的运输。胸腺表达的趋化因子（TECK或Ck β -15/CCL25）通过趋化因子受体CCR9发出信号，在胸腺和小肠中组成性表达，但在结肠中不表达，并且化学吸引了一小部分共表达整合素的pbl (4) β(7)。在这里，我们发现TECK在人小肠中表达，而不是在结肠中表达，在肠隐窝和肠固有层的内皮细胞和一部分细胞中表达，CCR9在大多数新鲜分离的小肠固有层单核细胞（LPMC）中表达，并且与结肠LPMC或PBL相比，其表达水平明显更高，TECK在体外对小肠有选择性趋化作用，但在结肠LPMC中没有。teck诱导的趋化性对百日咳毒素敏感，部分被抗体对CCR9抑制。TECK主要吸引小肠LPMC的T细胞部分，而分选的CD3(+)CCR9（+）和CD3(+)CCR9（-）淋巴细胞在单细胞水平产生相似的Th1或Th2细胞因子。总的来说，我们的数据表明，TECK在小肠中的选择性表达是CCR9（+）肠道记忆T细胞归巢到小肠而不是结肠的基础。这种区域专门化意味着小肠与结肠免疫反应的分离。
Chemokines play an important role in the migration of leukocytes at sites of inflammation, and some constitutively expressed chemokines may direct lymphocyte trafficking within lymphoid organs and peripheral tissues. Thymus-expressed chemokine (TECK or Ck beta -15/CCL25), which signals through the chemokine receptor CCR9, is constitutively expressed in the thymus and small intestine but not colon, and chemoattracts a small fraction of PBLs that coexpress the integrin alpha (4)beta (7). Here we show that TECK is expressed in the human small bowel but not colon by endothelial cells and a subset of cells in intestinal crypts and lamina propria, CCR9 is expressed in the majority of freshly isolated small bowel lamina propria mononuclear cells (LPMC) and at significantly higher levels compared with colonic LPMC or PBL, TECK was selectively chemotactic for small bowel but not colonic LPMC in vitro. The TECK-induced chemotaxis was sensitive to pertussis toxin and partially inhibited by Abs to CCR9. TECK attracts predominantly the T cell fraction of small bowel LPMC, whereas sorted CD3(+)CCR9(+) and CD3(+)CCR9(-) lymphocytes produce similar Th1 or Th2 cytokines at the single cell level. Collectively, our data suggest that the selective expression of TECK in the small bowel underlie the homing of CCR9(+) intestinal memory T cells to the small bowel rather than to the colon. This regional specialization implies a segregation of small intestinal from colonic immune responses.