Soilleux Elizabeth J, Morris Lesley S, Leslie George, Chehimi Jihed, Luo Qi, Levroney Ernest, Trowsdale John, Montaner Luis J, Doms Robert W, Weissman Drew, Coleman Nicholas, Lee Benhur
Department of Molecular Histopathology, University of Cambridge, United Kingdom.
J Leukoc Biol. 2002 Mar;71(3):445-57.
DC-SIGN is a C-type lectin, highly expressed on the surface of immature dendritic cells (DCs), that mediates efficient infection of T cells in trans by its ability to bind HIV-1, HIV-2, and SIV. In addition, the ability of DC-SIGN to bind adhesion molecules on surfaces of naïve T cells and endothelium also suggests its involvement in T-cell activation and DC trafficking. To gain further insights into the range of expression and potential functions of DC-SIGN, we performed a detailed analysis of DC-SIGN expression in adult and fetal tissues and also analyzed its regulated expression on cultured DCs and macrophages. First, we show that DC-SIGN expression is restricted to subsets of immature DCs in tissues and on specialized macrophages in the placenta and lung. There were no overt differences between DC-SIGN expression in adult and fetal tissues except that DC-SIGN expression in alveolar macrophages was only present after birth. Similarly, in tissues, DC-SIGN was observed primarily on immature (CD83-negative) DCs. Secondly, in the peripheral blood, we found expression of DC-SIGN on a small subset of BDCA-2+ plasmacytoid DC precursors (pDC2), concordant with our finding of large numbers of DC-SIGN-positive cells in allergic nasal polyps (previously shown to be infiltrated by DC2). Triple-label confocal microscopy indicated that DC-SIGN was colocalized with BDCA-2 and CD123 on DCs in nasal polyp tissue. Consistent with this finding is our observation that DC-SIGN can be up-regulated on monocyte-derived macrophages upon exposure to the Th2 cytokine, IL-13. In summary, our data demonstrate the relevant populations of DC and macrophages that express DC-SIGN in vivo where it may impact the efficiency of virus infection and indicate that DC-SIGN expression may be involved in the Th2 axis of immunity.
DC-SIGN是一种C型凝集素，在未成熟树突状细胞（DC）表面高度表达，它通过结合HIV-1、HIV-2和SIV的能力介导T细胞的有效反式感染。此外，DC-SIGN结合幼稚T细胞和内皮细胞表面粘附分子的能力也表明它参与T细胞活化和DC迁移。为了进一步深入了解DC-SIGN的表达范围和潜在功能，我们对成人和胎儿组织中DC-SIGN的表达进行了详细分析，并分析了其在培养的DC和巨噬细胞上的调控表达。首先，我们发现DC-SIGN的表达局限于组织中未成熟DC的亚群以及胎盘和肺中的特殊巨噬细胞。成人和胎儿组织中DC-SIGN的表达没有明显差异，只是肺泡巨噬细胞中的DC-SIGN表达仅在出生后出现。同样，在组织中，DC-SIGN主要在未成熟（CD83阴性）DC上观察到。其次，在外周血中，我们发现DC-SIGN在一小部分BDCA-2+浆细胞样DC前体（pDC2）上表达，这与我们在过敏性鼻息肉中发现大量DC-SIGN阳性细胞（先前显示被DC2浸润）的结果一致。三重标记共聚焦显微镜显示，DC-SIGN与鼻息肉组织中DC上的BDCA-2和CD123共定位。与这一发现一致的是，我们观察到单核细胞衍生的巨噬细胞在暴露于Th2细胞因子IL-13后，DC-SIGN可以上调。总之，我们的数据证明了在体内表达DC-SIGN的DC和巨噬细胞的相关群体，在那里它可能影响病毒感染的效率，并表明DC-SIGN表达可能参与免疫的Th2轴。
