Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction.
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.
Cao
Wei
W
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Bover
Laura
L
Cho
Minkwon
M
Wen
Xiaoxia
X
Hanabuchi
Shino
S
Bao
Musheng
M
Rosen
David B
DB
Wang
Yi-Hong
YH
Shaw
Joanne L
JL
Du
Qiumei
Q
Li
Chun
C
Arai
Naoko
N
Yao
Zhengbin
Z
Lanier
Lewis L
LL
Liu
Yong-Jun
YJ
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
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