The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20090547
The Journal of Experimental Medicine, Vol. 206, No. 7, 1603-1614
The Rockefeller University Press, 0022-1007 $30.00
© Cao et al.
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ARTICLE

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

Wei Cao1, Laura Bover1, Minkwon Cho3, Xiaoxia Wen2, Shino Hanabuchi1, Musheng Bao1, David B. Rosen4, Yi-Hong Wang1, Joanne L. Shaw1, Qiumei Du1, Chun Li2, Naoko Arai3, Zhengbin Yao5, Lewis L. Lanier4, and Yong-Jun Liu1

1 Department of Immunology, 2 Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054
3 SBI Biotech Co., Ltd., Ginkgo Biomedical Research Institute, Kawasaki 216-0001, Japan
4 Department of Microbiology and Immunology and the Cancer Research Institute, University of California at San Francisco, San Francisco, CA 94143
5 Genentech, Inc., South San Francisco, CA 94080

CORRESPONDENCE Wei Cao: wcao{at}mdanderson.org OR Yong-Jun Liu: yjliu{at}mdanderson.org

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–Fc{epsilon}RI{gamma} 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.

D.B. Rosen’s present address is Nodality, Inc., South San Francisco, CA 94080.

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.

© 2009 Cao et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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