Distribution and kinetics of SR-PSOX/CXCL16 and CXCR6 expression on human dendritic cell subsets and CD4+ T cells

Distribution and kinetics of SR-PSOX/CXCL16 and CXCR6 expression on human dendritic cell subsets and CD4+ T cells
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DOI:
10.1189/jlb.1204733
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发表时间:
2005-05-01
影响因子:
5.5
通讯作者:
Uchiyama, T
Uchiyama, T
中科院分区:
医学3区
文献类型:
--
作者:
Tabata, S;Kadowaki, N;Uchiyama, T

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树突状细胞(DC)通过产生T细胞吸引趋化因子和诱导T细胞上趋化因子受体的表达来协调T细胞应答。磷脂酰丝氨酸和氧化脂蛋白清道夫受体(SR-PSOX)/CXC趋化因子配体16(CXCL 16)是一种独特的趋化因子,也是一种内吞受体和粘附分子。SR-PSOX/CXCL 16是CXC趋化因子受体6(CXCR 6)的唯一已知配体,其在活化的T细胞上表达,因此可能在增强T细胞的效应子功能中起重要作用。在这里,我们研究了SR-PSOX/CXCL 16在人DC亚群上的表达和CXCR 6在T细胞亚群上的表达,以阐明DC/T细胞应答中CXCL 16/CXCR 6相互作用的动力学。膜结合SR-PSOX/CXCL 16在巨噬细胞、单核细胞来源的DC和Mood髓样DC上表达,并且在DC成熟后表达增加。髓系抗原呈递细胞组成性分泌SR-PSOX/CXCL 16持续较长时间,表明CXCL 16参与外周和淋巴组织。浆细胞样DC在其表面上几乎不表达SR-PSOX/CXCL 16,但分泌显著量的SR-PSOX/CXCL 16。CD 4(+)效应记忆T(T-EM)细胞的亚群组成性表达CXCR 6,而中枢记忆T细胞(T-CM)和初始T细胞不表达。然而,在用成熟DC刺激后,T-CM细胞上CXCR 6的表达显著上调,而幼稚T细胞上的表达仅被微弱地诱导。这些结果表明,SR-PSOX/CXCL 16和CXCR 6之间的相互作用在增强淋巴组织中成熟DC的T-CM细胞应答和增强外周炎症组织中巨噬细胞的T-EM细胞应答中起重要作用。
Dendritic cells (DCs) coordinate T cell responses by producing T cell-attracting chemokines and by inducing the expression of chemokine receptors on T cells. Scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXC chemokine ligand 16 (CXCL16) is a unique chemokine that also functions as an endocytic receptor and an adhesion molecule in its membrane-hound form. SR-PSOX/CXCL16 is the only known ligand of CXC chemokine receptor 6 (CXCR6) that is expressed on activated T cells and thus, may play an important role in enhancing effector functions of T cells. Here, we investigated the expression of SR-PSOX/CXCL16 on human DC subsets and that of CXCR6 on T cell subpopulations to elucidate the dynamics of CXCL16/CXCR6 interaction in DC/T cell responses. Membrane-bound SR-PSOX/CXCL16 was expressed on macrophages, monocyte-derived DCs, and Mood myeloid DCs, and the expression increased after DC maturation. Myeloid antigen-presenting cells constitutively secreted SR-PSOX/CXCL16 for an extended period, suggesting the involvement of CXCL16 in peripheral and lymphoid tissues. Plasmacytoid DCs hardly expressed SR-PSOX/CXCL16 on their surfaces but secreted significant amounts of SR-PSOX/CXCL16. A subset of CD4(+) effector memory T (T-EM) Cells Constitutively expressed CXCR6, whereas central memory T cells (T-CM) and naive T cells did not. Upon stimulation,with mature DCs, however, the expression of CXCR6 on T-CM cells was markedly up-regulated, whereas the expression on naive T cells was induced only weakly. These results suggest that the interaction between SR-PSOX/CXCL16 and CXCR6 plays an important role in enhancing T-CM cell responses by mature DCs in lymphoid tissues and in augmenting T-EM cell responses by macro phages in peripheral inflamed tissues.