Epithelial inflammation is associated with CCL28 production and the recruitment of regulatory T cells expressing CCR10
Epithelial inflammation is associated with CCL28 production and the recruitment of regulatory T cells expressing CCR10
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DOI：
10.4049/jimmunol.177.1.593
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Adams, David H.
中科院分区：
文献类型：
--
作者：
Eksteen, Bertus;Miles, Alice;Adams, David H.
黏膜组织需要持续的免疫监测，以清除有害病原体，同时保持对自身AGS的耐受性。调节性T细胞(Tregs)在这一过程中起着核心作用，据报道，α(E)β(7)的表达定义了Tregs的一个亚群，与炎症组织有趋向性。然而，负责将Treg募集到上皮细胞表面的信号知之甚少。我们已经从慢性炎症的人类肝脏中分离出表达CCR10的CD25(+)、CD4(+)、Foxp3(+)Tregs的一个子集，这些Tregs具有强大的抗炎特性。胆管周围检测到CCR10(+)Tregs，表达CCR10配体CCL28水平升高。CCL28是由原代人胆管细胞在体外对内毒素、IL-1β或胆汁酸的反应而分泌的。CCR10(+)Tregs体外暴露于CCL28可刺激细胞黏附分子-1和黏附分子-1的迁移和黏附。肝脏来源的CCR10(+)Tregs低水平表达CCR7，但高水平表达CXCR3，CXCR3是一种与炎症组织渗透相关的趋化因子受体，包含α(E)β(+)(7)细胞亚群。我们认为，CXCR3促进Tregs在炎症组织中的募集，而CCR10允许炎症组织对上皮细胞分泌的CCL28产生反应，导致CCR10(+)Tregs在粘膜表面积聚。
Mucosal tissues require constant immune surveillance to clear harmful pathogens while maintaining tolerance to self Ags. Regulatory T cells (Tregs) play a central role in this process and expression of alpha(E)beta(7) has been reported to define a subset of Tregs with tropism for inflamed tissues. However, the signals responsible for recruiting Tregs to epithelial surfaces are poorly understood. We have isolated a subset of CCR10-expressing CD25(+)CD4(+)Foxp3(+) Tregs with potent anti-inflammatory properties from chronically inflamed human liver. The CCR10(+) Tregs were detected around bile ducts that expressed increased levels of the CCR10 ligand CCL28. CCL28 was secreted by primary human cholangiocytes in vitro in response to LPS, IL-1 beta, or bile acids. Exposure of CCR10(+) Tregs to CCL28 in vitro stimulated migration and adhesion to mucosal addressin cell adhesion molecule-1 and VCAM-1. Liver-derived CCR10(+) Tregs expressed low levels of CCR7 but high levels of CXCR3, a chemokine receptor associated with infiltration into inflamed tissue and contained a subset of alpha(E)beta(+)(7) cells. We propose that CXCR3 promotes the recruitment of Tregs to inflamed tissues and CCR10 allows them to respond to CCL28 secreted by epithelial cells resulting in the accumulation of CCR10(+) Tregs at mucosal surfaces.