Cutting edge: Critical role of CXCL16/CXCR6 in NKT cell trafficking in allograft tolerance
Cutting edge: Critical role of CXCL16/CXCR6 in NKT cell trafficking in allograft tolerance
复制标题
DOI：
10.4049/jimmunol.175.4.2051
复制
发表时间：
2005-08-15
影响因子：
4.4
通讯作者：
Seino, K
中科院分区：
文献类型：
--
作者：
Jiang, XF;Shimaoka, T;Seino, K
趋化因子或其受体在移植物排斥反应中起着重要的作用。然而，趋化因子及其受体在维持移植耐受中的作用尚不清楚。在这项研究中，我们证明，阻断V α 14(+) NKT细胞上高度表达的趋化因子受体CXCR6与其配体CXCL16之间的相互作用，导致移植物耐受维持失败，从而诱导移植物排斥加速。在小鼠移植耐受模型中，CXCL16在耐受的同种异体移植物中表达上调，抗CXCL16单抗抑制了NKT细胞在移植体内的积累。体外实验进一步表明，阻断CXCL16/CXCR6相互作用不仅显著影响NKT细胞的趋化性，而且显著影响细胞粘附。这些结果证明了CYCL16和CXCR6分子在NKT细胞介导的心脏异体移植耐受维持中的独特作用。
It is well-documented that certain chemokines or their receptors play important roles in the graft rejection. However, the roles of chemokines and their receptors in the maintenance of transplantation tolerance remain unclear. In this study, we demonstrate that blocking of the interaction between the chemokine receptor, CXCR6, highly expressed on V alpha 14(+) NKT cells and its ligand, CXCL16, resulted in the failure to maintain graft tolerance and thus in the induction of acceleration of graft rejection. In a mouse transplant tolerance model, the expression of CXCL16 was up-regulated in the tolerated allografts, and anti-CXCL16 mAb inhibited intragraft accumulation of NKT cells. In vitro experiments further showed that blocking of CXCL16/CXCR6 interaction significantly affected not only chemotaxis but also cell adhesion of NKT cells. These results demonstrate the unique role of CYCL16 and CXCR6 molecules in the maintenance of cardiac allograft tolerance mediated by NKT cells.