title: BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells.
abstract: 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.
authors.affiliation: Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. wcao@mdacc.tmc.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: David B
authors.initials: DB
authors.lastname: Rosen
authors.forename: Laura
authors.initials: L
authors.lastname: Bover
authors.forename: Gokuran
authors.initials: G
authors.lastname: Watanabe
authors.forename: Musheng
authors.initials: M
authors.lastname: Bao
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: 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*
chemical_list: 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