A transmembrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion
A transmembrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion
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DOI：
10.1093/intimm/dxh369
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发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Shimizu, A
中科院分区：
文献类型：
--
作者：
Hara, T;Katakai, T;Shimizu, A
淋巴组织中的基质细胞提供触发有效免疫反应所需的微环境场。纤维母细胞网状细胞（FRCs）是这种基质场的组成部分之一；它们构建网状网络，被认为调节免疫细胞的行为。然而，介导淋巴细胞和FRCs之间相互作用的因素尚不清楚。在这里，我们展示了小鼠淋巴结（LN）来源的FRC细胞系BLS4表达跨膜趋化因子CXC趋化因子配体（CXCL） 16，以响应肿瘤坏死因子α (TNF α)和IFN γ。TNF α诱导的CXCL16表达依赖于NF κ B、p38 MAPK和PKA。基质金属蛋白酶活性是在培养上清中产生可溶性CXCL16所必需的，可能是通过在细胞外区域的近膜区域脱落。IL-12在抗cd3 / cd28刺激的CD8(+) T细胞中增强CXCR6的表达，并以TNF α依赖的方式增强其与BLS4细胞表面的粘附。在抗cxcl16和抗血管细胞粘附分子1 （VCAM-1）抗体的存在下，这种粘附被显著抑制。在LN切片的FRCs和从LNs分离的gp38(+)VCAM-1(+) FRCs中也检测到CXCL16的表达。综上所述，这些发现表明CXCL16是淋巴组织中淋巴细胞-基质相互作用的重要介质。
Stromal cells in lymphoid tissues provide microenvironmental fields required for the triggering of efficient immune responses. Fibroblastic reticular cells (FRCs) are one of the integral constituents of such stromal fields; they construct the reticular network and are considered to regulate immune cells' behavior. However, the factors that mediate the interaction between lymphocytes and FRCs are poorly understood. Here we show that a mouse lymph node (LN)-derived FRC cell line, BLS4, expresses a transmembrane chemokine, CXC chemokine ligand (CXCL) 16, in response to tumor necrosis factor alpha (TNF alpha) and IFN gamma. TNF alpha-induced expression of CXCL16 depends on NF kappa B, p38 MAPK and PKA. Matrix metalloproteinase activity is required for producing soluble CXCL16 in the culture supernatant, likely via shedding at the juxtamembrane region of the extracellular domain. IL-12 enhances the expression of CXCR6 in anti-CD3/CD28-stimulated CD8(+) T cells and their adhesion to the BLS4 cell surface in a TNF alpha-dependent fashion. The adherence is significantly inhibited in the presence of both anti-CXCL16 and anti-vascular cell adhesion molecule 1 (VCAM-1) antibodies. CXCL16 expression is also detected in the FRCs in LN sections and in gp38(+)VCAM-1(+) FRCs isolated from LNs. Taken together, these findings suggest that CXCL16 is an important mediator of lymphocyte-stromal interaction within lymphoid tissues.