Regulation of TLR 7 / 9 responses in plasmacytoid dendritic cells by BST 2 and ILT 7 receptor interaction

The Rockefeller University Press $30.00 J. Exp. Med. Vol. 206 No. 7 1603-1614 www.jem.org/cgi/doi/10.1084/jem.20090547 1603 In humans and other mammals, plasmacytoid DCs (pDCs) are specialized immune cells that selectively express Toll-like receptor (TLR) 7 and TLR9, which are key endosomal sensors of microbial and self-RNA or DNA, respectively (Jarrossay et al., 2001; Kadowaki et al., 2001; Liu, 2005; Gilliet et al., 2008). Activation of TLR7 or TLR9 by nucleic acids in pDCs triggers signal transduction, leading to rapid and robust secretion of type I IFN, inflammatory cytokines, and chemokines (Colonna et al., 2004; Honda and Taniguchi, 2006; Kawai and Akira, 2006; Piqueras et al., 2006; Gilliet et al., 2008). The TLR-induced IFN response is regulated by several immunoreceptor tyrosine-based activation motif (ITAM)– bearing signaling receptors on pDCs (Novak et al., 2004; Fuchs et al., 2005; Blasius et al., 2006a; Cao et al., 2006, 2007; Röck et al., 2007; Cho et al., 2008; Gilliet et al., 2008). One such receptor is ILT7, a member of the Ig-like transcript (ILT) family (also known as leukocyte Ig-like receptors) found in humans and primates (Brown et al., 2004). ILTs, which are expressed by a variety of immune cell types, are comprised of a group of inhibitory receptors bearing immunoreceptor tyrosine-based inhibitory motifs and a group of stimulatory receptors that signal through their association with adaptor molecules containing ITAM (Brown et al., 2004). ILT7, also known as LILRA4 and CD85g, contains four extracellular Ig-like domains and a positively charged residue within the transmembrane region, allowing ILT7 to form a receptor complex with a signaling adaptor FcRI. Uniquely expressed by human pDCs, ILT7 suppresses TLR7/9-induced type I IFN secretion by pDCs when cross-linked by anti-ILT7 mAbs that trigger signaling activation (Cao et al., 2006; CORRESPONDENCE Wei Cao: wcao@mdanderson.org OR Yong-Jun Liu: yjliu@mdanderson.org

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