title: Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction.
abstract: Plasmacytoid dendritic cells (pDCs) produce copious type I interferon (IFN) upon sensing nucleic acids through Toll-like receptor (TLR) 7 and TLR9. Uncontrolled pDC activation and IFN production are implicated in lymphopenia and autoimmune diseases; therefore, a mechanism controlling pDC IFN production is essential. Human pDCs specifically express an orphan receptor, immunoglobulin-like transcript 7 (ILT7). Here, we discovered an ILT7 ligand expressed by human cell lines and identified it as bone marrow stromal cell antigen 2 (BST2; CD317). BST2 directly binds to purified ILT7 protein, initiates signaling via the ILT7-FcepsilonRIgamma complex, and strongly inhibits production of IFN and proinflammatory cytokines by pDCs. Readily induced by IFN and other proinflammatory cytokines, BST2 may modulate the human pDC's IFN responses through ILT7 in a negative feedback fashion.
authors: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors: Wei
authors: W
authors: Cao
authors: Laura
authors: L
authors: Bover
authors: Minkwon
authors: M
authors: Cho
authors: Xiaoxia
authors: X
authors: Wen
authors: Shino
authors: S
authors: Hanabuchi
authors: Musheng
authors: M
authors: Bao
authors: David B
authors: DB
authors: Rosen
authors: Yi-Hong
authors: YH
authors: Wang
authors: Joanne L
authors: JL
authors: Shaw
authors: Qiumei
authors: Q
authors: Du
authors: Chun
authors: C
authors: Li
authors: Naoko
authors: N
authors: Arai
authors: Zhengbin
authors: Z
authors: Yao
authors: Lewis L
authors: LL
authors: Lanier
authors: Yong-Jun
authors: YJ
authors: Liu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D058851:GPI-Linked Proteins; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D058851:GPI-Linked Proteins; D016898:Interferon-alpha; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C488262:LILRA4 protein, human; C495348:TLR7 protein, human; C495371:TLR9 protein, human