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Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction

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–FcϵRIγ 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. Footnotes Abbreviations used: BST2, bone marrow stromal cell antigen 2; ILT, Ig-like transcript; ITAM, immunoreceptor tyrosine-based activation motif; MOI, multiplicity of infection; pDC, plasmacytoid DC; TLR, Toll-like receptor. Submitted: 10 March 2009 Accepted: 8 June 2009 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction

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Publisher
Rockefeller University Press
Copyright
© 2009 Cao et al.
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.20090547
pmid
19564354
Publisher site
See Article on Publisher Site

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–FcϵRIγ 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. Footnotes Abbreviations used: BST2, bone marrow stromal cell antigen 2; ILT, Ig-like transcript; ITAM, immunoreceptor tyrosine-based activation motif; MOI, multiplicity of infection; pDC, plasmacytoid DC; TLR, Toll-like receptor. Submitted: 10 March 2009 Accepted: 8 June 2009

Journal

The Journal of Experimental Medicine – Rockefeller University Press

Published: Jul 6, 2009

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