Journal
BLOOD
Volume 107, Issue 6, Pages 2474-2476Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-09-3746
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Funding
- NCI NIH HHS [R01CA109673-01A1, P30 CA091842, P30 CA91842] Funding Source: Medline
- PHS HHS [2T32A10717226] Funding Source: Medline
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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 (lg)-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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