The membrane-bound chemokine CXCL16 expressed on follicle-associated epithelium and m cells mediates lympho-epithelial interaction in GALT
The membrane-bound chemokine CXCL16 expressed on follicle-associated epithelium and m cells mediates lympho-epithelial interaction in GALT
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DOI：
10.4049/jimmunol.176.1.43
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Ohno, H
中科院分区：
文献类型：
--
作者：
Hase, K;Murakami, T;Ohno, H
CXCL 16是一种跨膜粘附分子，同时也是一种可溶性趋化因子。在这项研究中，我们发现，CXCL 16的mRNA和蛋白质的组成性表达的滤泡相关上皮细胞覆盖派尔集合淋巴结（PP），孤立的淋巴滤泡，盲肠补丁，但最低限度的绒毛上皮在小鼠胃肠道。CXCL 16受体CXCR 6/Bonzo在从PP分离的CD 4（+）和CD 8（+）T细胞亚群上组成性表达。用抗CD 3和抗CD 28单克隆抗体刺激PP T细胞后，PP T细胞上CXCR 6/Bonzo的表达上调。活化的PP T细胞表现出响应于CXCL 16的可溶性N-末端趋化因子结构域的趋化性迁移。此外，活化的PP T细胞选择性地粘附于表达鼠CXCL 16的细胞。为了确定CXCL 16在GALT中的生理作用，我们首先仔细分析了PP中的T细胞分布。T细胞不仅分布于滤泡间区，而且以较少的频率分布于上皮下圆顶（SED）和淋巴滤泡的生发中心。因此，大多数过继转移的活化T细胞迁移到SED和滤泡间区。然而，CXCL 16的中和特异性地减少了过继、转移、活化的T细胞向PP的SED中的迁移。这些数据表明，CXCL 16上表达的卵泡相关上皮细胞中起着重要的作用，在招聘和保留的活化T细胞的SED，并应至少部分负责淋巴细胞区室化GALT。
The recently identified CXCL16 has dual functions as a transmembrane adhesion molecule and a soluble chemokine. In this study we found that CXCL16 mRNA and protein were expressed constitutively on the follicle-associated epithelium covering Peyer's patches (PPs), isolated lymphoid follicles, and cecal patches, but minimally on the villous epithelium in the murine gastrointestinal tract. The CXCL16 receptor CXCR6/Bonzo was constitutively expressed on subpopulations of CD4(+) and CD8(+) T cells isolated from PPs. The expression of CXCR6/Bonzo on the PP T cells was up-regulated after stimulation with anti-CD3 and anti-CD28 mAbs. The activated PP T cells showed chemotactic migration in response to the soluble N-terminal chemokine domain of CXCL16. Furthermore, the activated PP T cells selectively adhered to cells expressing murine CXCL16. To determine the physiological role of CXCL16 in GALT, we first carefully analyzed T cell distribution in PPs. T cells localized not only in the interfollicular region but also at a lesser frequency in the subepithelial dome (SED) and in the germinal center of lymphoid follicles. Consistently, the majority of the adoptive transferred activated T cells migrated into the SED and the interfollicular region. However, the neutralization of CXCL16 specifically reduced the migration of the adoptive, transferred, activated T cells into the SED of PPs. These data suggest that CXCL16 expressed on the follicle-associated epithelium plays an important role in the recruitment and retention of activated T cells in the SED and should, at least partially, be responsible for lymphocyte compartmentalization in GALT.