Constitutive and induced expression of DC‐SIGN on dendritic cell and macrophage subpopulations in situ and in vitro
Constitutive and induced expression of DC‐SIGN on dendritic cell and macrophage subpopulations in situ and in vitro
复制标题
DOI：
10.1189/jlb.71.3.445
复制
发表时间：
2002-03
影响因子：
5.5
通讯作者：
E. Soilleux;L. Morris;G. Leslie;J. Chehimi;Qi Luo;Ernest L. Levroney;J. Trowsdale;L. Montaner;R. Doms;D. Weissman;N. Coleman;Benhur Lee
中科院分区：
文献类型：
--
作者：
E. Soilleux;L. Morris;G. Leslie;J. Chehimi;Qi Luo;Ernest L. Levroney;J. Trowsdale;L. Montaner;R. Doms;D. Weissman;N. Coleman;Benhur Lee
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，通过其结合HIV‐1、HIV‐2和SIV的能力介导T细胞的有效感染。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其参与T细胞活化和DC运输。为了进一步了解DC-SIGN的表达范围和潜在功能，我们对成人和胎儿组织中的DC-SIGN表达进行了详细分析，并分析了其在培养的DC和巨噬细胞中的调节表达。首先，我们发现DC-SIGN表达仅限于组织中未成熟DC的亚群以及胎盘和肺中的特化巨噬细胞。成人和胎儿组织中的DC-SIGN表达没有明显差异，除了肺泡巨噬细胞中的DC-SIGN表达仅在出生后存在。类似地，在组织中，主要在未成熟（CD 83阴性）DC上观察到DC-SIGN。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（pDC 2）上表达，这与我们在过敏性鼻息肉中发现的大量DC-SIGN阳性细胞（先前显示被DC 2浸润）一致。三重标记共聚焦显微镜表明，DC-SIGN与BDCA-2和CD 123共定位于鼻息肉组织中的DC上。与这一发现相一致的是，我们观察到DC‐SIGN可以在暴露于Th 2细胞因子IL‐13后在单核细胞衍生的巨噬细胞上上调。总之，我们的数据证明了体内表达DC-SIGN的DC和巨噬细胞的相关群体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Th 2轴。
DC‐SIGN is a C‐type lectin, highly expressed on the surface ofimmature dendritic cells (DCs), that mediates efficient infection of Tcells in trans by its ability to bind HIV‐1, HIV‐2, and SIV. Inaddition, the ability of DC‐SIGN to bind adhesion molecules on surfacesof naïve T cells and endothelium also suggests its involvementin T‐cell activation and DC trafficking. To gain further insights intothe range of expression and potential functions of DC‐SIGN, weperformed a detailed analysis of DC‐SIGN expression in adult and fetaltissues and also analyzed its regulated expression on cultured DCs andmacrophages. First, we show that DC‐SIGN expression is restricted tosubsets of immature DCs in tissues and on specialized macrophages inthe placenta and lung. There were no overt differences between DC‐SIGNexpression in adult and fetal tissues except that DC‐SIGN expression inalveolar macrophages was only present after birth. Similarly, intissues, DC‐SIGN was observed primarily on immature (CD83‐negative)DCs. Secondly, in the peripheral blood, we found expression of DC‐SIGNon a small subset of BDCA‐2+ plasmacytoid DC precursors (pDC2),concordant with our finding of large numbers of DC‐SIGN‐positive cellsin allergic nasal polyps (previously shown to be infiltrated by DC2).Triple‐label confocal microscopy indicated that DC‐SIGN was colocalizedwith BDCA‐2 and CD123 on DCs in nasal polyp tissue. Consistent withthis finding is our observation that DC‐SIGN can be up‐regulated onmonocyte‐derived macrophages upon exposure to the Th2 cytokine, IL‐13. In summary, our data demonstrate the relevant populations of DC andmacrophages that express DC‐SIGN in vivo where it may impact theefficiency of virus infection and indicate that DC‐SIGN expression maybe involved in the Th2 axis of immunity.