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 product...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2009-07, Vol.206 (7), p.1603-1614
Main Authors: Cao, Wei, Bover, Laura, Cho, Minkwon, Wen, Xiaoxia, Hanabuchi, Shino, Bao, Musheng, Rosen, David B, Wang, Yi-Hong, Shaw, Joanne L, Du, Qiumei, Li, Chun, Arai, Naoko, Yao, Zhengbin, Lanier, Lewis L, Liu, Yong-Jun
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - genetics
Antigens, CD - immunology
Cell Line
Cell Line, Tumor
Cytokines - immunology
Dendritic Cells - cytology
Dendritic Cells - immunology
GPI-Linked Proteins
Humans
Immunity, Innate - immunology
Interferon-alpha - immunology
Ligands
Membrane Glycoproteins - genetics
Membrane Glycoproteins - immunology
Mice
Mice, Inbred BALB C
Receptors, Immunologic - genetics
Receptors, Immunologic - immunology
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - immunology
Signal Transduction - immunology
Toll-Like Receptor 7 - genetics
Toll-Like Receptor 7 - immunology
Toll-Like Receptor 9 - genetics
Toll-Like Receptor 9 - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20090547