Cao Wei, Zhang Li, Rosen David B, Bover Laura, Watanabe Gokuran, Bao Musheng, Lanier Lewis L, Liu Yong-Jun
Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
PLoS Biol. 2007 Sep 11;5(10):e248. doi: 10.1371/journal.pbio.0050248.
Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs) uniquely express blood dendritic cell antigen 2 (BDCA2) protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter Fc epsilon RI gamma. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR), which is distinct from the system involved in T cell receptor (TCR) signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with Fc epsilon RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs.
树突状细胞配备有凝集素受体，以感知细胞外环境并调节细胞反应。人类浆细胞样树突状细胞（pDCs）独特地表达血液树突状细胞抗原2（BDCA2）蛋白，这是一种缺乏可识别信号基序的C型凝集素。我们在此证明，BDCA2与跨膜衔接蛋白FcεRIγ形成复合物。通过通路分析，我们在人类pDCs中鉴定出一种全面的信号传导机制，类似于在B细胞受体（BCR）下游起作用的机制，这与T细胞受体（TCR）信号传导所涉及的系统不同。BDCA2交联导致类似BCR的级联反应激活，这有力地抑制了pDCs对Toll样受体配体产生I型干扰素和其他细胞因子的能力。因此，通过与FcεRIγ结合，BDCA2激活一种新型的类似BCR的信号通路来调节pDCs的免疫功能。
