Journal
PLOS BIOLOGY
Volume 5, Issue 10, Pages 2190-2200Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.0050248
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Funding
- NIAID NIH HHS [R01 AI068129, AI068129] Funding Source: Medline
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Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs) uniquely express blood dendritic cell antigen 2 (BDCA2) protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter Fc epsilon Rl gamma. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR), which is distinct from the system involved in T cell receptor (TCR) signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with Fc epsilon Rl gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs.
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