TY - JOUR
T1 - Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12
AU - Blasius, Amanda L.
AU - Cella, Marina
AU - Maldonado, Jorge
AU - Takai, Toshiyuki
AU - Colonna, Marco
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/3/15
Y1 - 2006/3/15
N2 - Natural interferon (IFN)-producing cells are the primary cell type responsible for production of type I IFN in response to viruses. Herein we report the identification of the first molecular marker of mouse natural interferon-producing cells (IPCs), a novel member of the sialic acid-binding immunoglobulin (Ig)-like lectin (Siglec) family termed Siglec-H. Siglec-H is expressed exclusively on IPCs and is unique among Siglec proteins in that it associates with the adaptor protein DAP12. Moreover, we show that DAP12 modulates the type I IFN response of IPCs to a Toll-like receptor 9 (TLR9) agonist. This observation explains our previous finding that stimulation of IPCs with 440c, a Siglec-H-specific antibody, reduces IPC secretion of type I IFN. Moreover, it supports a model in which engagement of DNAX-activation protein 12 (DAP12)-associated receptors with antibodies or low avidity endogenous ligands interferes with TLR-mediated cellular activation.
AB - Natural interferon (IFN)-producing cells are the primary cell type responsible for production of type I IFN in response to viruses. Herein we report the identification of the first molecular marker of mouse natural interferon-producing cells (IPCs), a novel member of the sialic acid-binding immunoglobulin (Ig)-like lectin (Siglec) family termed Siglec-H. Siglec-H is expressed exclusively on IPCs and is unique among Siglec proteins in that it associates with the adaptor protein DAP12. Moreover, we show that DAP12 modulates the type I IFN response of IPCs to a Toll-like receptor 9 (TLR9) agonist. This observation explains our previous finding that stimulation of IPCs with 440c, a Siglec-H-specific antibody, reduces IPC secretion of type I IFN. Moreover, it supports a model in which engagement of DNAX-activation protein 12 (DAP12)-associated receptors with antibodies or low avidity endogenous ligands interferes with TLR-mediated cellular activation.
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U2 - 10.1182/blood-2005-09-3746
DO - 10.1182/blood-2005-09-3746
M3 - Article
C2 - 16293595
AN - SCOPUS:33644772437
VL - 107
SP - 2474
EP - 2476
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -