BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells.
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 RI 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 RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs.
Cao
Wei
W
Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. wcao@mdacc.tmc.edu
Zhang
Li
L
Rosen
David B
DB
Bover
Laura
L
Watanabe
Gokuran
G
Bao
Musheng
M
Lanier
Lewis L
LL
Liu
Yong-Jun
YJ
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D046912:Multiprotein Complexes / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; C443299:CLEC4C protein, human; D007370:Interferon Type I; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D011971:Receptors, Immunologic