King's College London, MRC Centre for Transplantation, NIHR Comprehensive Biomedical Research Centre, Guy's Hospital, London, UK.
Mol Immunol. 2011 May;48(9-10):1121-7. doi: 10.1016/j.molimm.2011.02.003. Epub 2011 Mar 23.
Integration of innate and adaptive arms of the immune response at a cellular and molecular level appears to be fundamental to the development of powerful effector functions in host defence and aberrant immune responses. Here we provide evidence that the functions of human complement activation and antigen presentation converge on dendritic cells (DCs). We show that several subsets of human DCs [i.e., monocyte derived (CD1a(+)CD14(-)), dermal (CD1a(+)DC-SIGN(+)), Langerhans (CD1a(+)Langerin(+)), myeloid (CD1c(+)CD19(-)), plamacytoid (CD45RA(+)CD123(+))] express many of the components of the classical and alternative and terminal pathways of complement. Moreover human DCs have receptors known to detect the biologically active peptides C3a and C5a (C3aR, C5aR) and the covalently bound fragments C3b and metabolites iC3b and C3d which serve in immune adhesion (i.e., CR3, CR4, CRIg). We also show that the human DC surface is characterised by membrane bound regulators of complement activation, which are also known to participate in intracellular signalling (i.e., CD46, CD55, CD59). This work provides an extensive description of complement components relevant to the integrated actions of complement and DC, illuminated by animal studies. It acts as a resource that allows further understanding and exploitation of role of complement in human health and immune mediated diseases.
在细胞和分子水平上，先天免疫和适应性免疫途径的整合，似乎对于宿主防御和异常免疫反应中强大效应功能的发展至关重要。在这里，我们提供了证据表明，人类补体激活和抗原呈递的功能集中在树突状细胞 (DCs) 上。我们表明，几种人类 DC 亚群 [即单核细胞衍生的 (CD1a(+)CD14(-))、皮肤 (CD1a(+)DC-SIGN(+))、朗格汉斯 (CD1a(+)Langerin(+))、髓样 (CD1c(+)CD19(-))、浆细胞样 (CD45RA(+)CD123(+))] 表达补体经典和替代途径以及末端途径的许多成分。此外，人类 DC 具有已知可检测生物活性肽 C3a 和 C5a（C3aR、C5aR）以及共价结合片段 C3b 和代谢物 iC3b 和 C3d 的受体，这些受体在免疫黏附中起作用（即 CR3、CR4、CRIg）。我们还表明，人 DC 表面的特征是补体激活的膜结合调节剂，这些调节剂也已知参与细胞内信号转导（即 CD46、CD55、CD59）。这项工作提供了与补体和 DC 的综合作用相关的补体成分的广泛描述，这一点通过动物研究得到了阐明。它作为一种资源，允许进一步理解和利用补体在人类健康和免疫介导疾病中的作用。
