Blasius Amanda L, Cella Marina, Maldonado Jorge, Takai Toshiyuki, Colonna Marco
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Blood. 2006 Mar 15;107(6):2474-6. doi: 10.1182/blood-2005-09-3746. Epub 2005 Nov 17.
Natural interferon (IFN)-producing cells are the primary cell type responsible for production of type I IFN in response to viruses. Herein we report the identification of the first molecular marker of mouse natural interferon-producing cells (IPCs), a novel member of the sialic acid-binding immunoglobulin (Ig)-like lectin (Siglec) family termed Siglec-H. Siglec-H is expressed exclusively on IPCs and is unique among Siglec proteins in that it associates with the adaptor protein DAP12. Moreover, we show that DAP12 modulates the type I IFN response of IPCs to a Toll-like receptor 9 (TLR9) agonist. This observation explains our previous finding that stimulation of IPCs with 440c, a Siglec-H-specific antibody, reduces IPC secretion of type I IFN. Moreover, it supports a model in which engagement of DNAX-activation protein 12 (DAP12)-associated receptors with antibodies or low avidity endogenous ligands interferes with TLR-mediated cellular activation.
天然干扰素（IFN）产生细胞是负责在病毒感染时产生I型干扰素的主要细胞类型。在此我们报告了小鼠天然干扰素产生细胞（IPC）首个分子标志物的鉴定，它是唾液酸结合免疫球蛋白（Ig）样凝集素（Siglec）家族的一个新成员，命名为Siglec-H。Siglec-H仅在IPC上表达，并且在Siglec蛋白中是独特的，因为它与接头蛋白DAP12相关联。此外，我们表明DAP12调节IPC对Toll样受体9（TLR9）激动剂的I型干扰素反应。这一观察结果解释了我们之前的发现，即用Siglec-H特异性抗体440c刺激IPC会减少IPC分泌I型干扰素。此外，它支持了一种模型，即DNAX激活蛋白12（DAP12）相关受体与抗体或低亲和力内源性配体的结合会干扰TLR介导的细胞激活。
