Recruitment of CCR6-Expressing Th17 Cells by CCL 20 Secreted from IL-1β-, TNF-α-, and IL-17A-Stimulated Endometriotic Stromal Cells
Recruitment of CCR6-Expressing Th17 Cells by CCL 20 Secreted from IL-1β-, TNF-α-, and IL-17A-Stimulated Endometriotic Stromal Cells
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DOI：
10.1210/en.2010-0398
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发表时间：
2010-11-01
期刊：
影响因子：
4.8
通讯作者：
Taketani, Yuji
中科院分区：
文献类型：
--
作者：
Hirata, Tetsuya;Osuga, Yutaka;Taketani, Yuji
在T细胞分化的新范例中，17型辅助性T细胞（Th 17）可能在子宫内膜异位症（一种慢性炎症性疾病）中发挥重要作用。然而，调节Th 17细胞在增生组织中积累的机制仍然未知。我们假设Th 17细胞通过趋化因子CC趋化因子配体（CCL）20及其受体CCR 6的相互作用迁移到增生组织。使用子宫内膜异位症患者的异位组织，我们通过流式细胞术证明，异位组织中的Th 17细胞表达CC趋化因子受体（CCR）6。免疫组化结果显示，CCL 20在上皮细胞和上皮下的基质细胞中均有表达。CCR 6+细胞小而圆，散在分布于间质中，间质中有丰富的CCL 20+细胞。在迁移测定中，CCL 20引起外周血中Th 17细胞的选择性迁移。IL-1 β、TNF-α和IL-17 A增加了培养的增生性基质细胞中CCL 20的分泌。p38-和p42/44-MAPK以及应激活化蛋白激酶/c-Jun激酶的抑制剂抑制IL-1 β、TNF-α和IL-17 A增加的CCL 20分泌。这表明CCL 20/CCR 6系统参与了Th 17细胞向子宫内膜异位组织的迁移，并且促炎细胞因子通过上调子宫内膜异位基质细胞的CCL 20分泌而促进子宫内膜异位症的发展。（内分泌学151：5468-5476，2010）
In a novel paradigm of T cell differentiation, type 17 T helper (Th17) cells may play a significant role in endometriosis, a chronic inflammatory disease. However, the mechanism regulating the accumulation of Th17 cells in endometriotic tissues remains unknown. We hypothesized that Th17 cells migrate to endometriotic tissues through an interaction of the chemokine CC chemokine ligand (CCL) 20 and its receptor CCR6. Using endometriotic tissues from women with endometriosis, we demonstrated, by flow cytometry, that Th17 cells in endometriotic tissues express CC chemokine receptor (CCR)6. Immunohistochemistry also revealed that CCL20 was expressed in the epithelial cells and stromal cells beneath the epithelium of endometriotic tissues. CCR6+ cells were small and round and scattered in the stroma in which abundant CCL20+ cells were detected. CCL20 caused selective migration of Th17 cells in the peripheral blood in a migration assay. IL-1 beta, TNF-alpha, and IL-17A increased the secretion of CCL20 in cultured endometriotic stromal cells. Inhibitors of p38- and p42/44-MAPKs, and stress-activated protein kinase/c-Jun kinase suppressed the secretion of CCL20 increased by IL-1 beta, TNF-alpha, and IL-17A. This suggests that the CCL20/CCR6 system is involved in the migration of Th17 cells to endometriotic tissues and that proinflammatory cytokines contribute to the development of endometriosis via up-regulation of CCL20 secretion from endometriotic stromal cells. (Endocrinology 151: 5468-5476, 2010)