title: Regulation of plasmacytoid dendritic cell responses by PIR-B.
abstract: Plasmacytoid dendritic cells (PDCs) produce type I interferons (IFNs) in response to viral nucleic acids to exert antiviral immunity. However, PDCs are related to the progress and severity of autoimmune diseases, such as systemic lupus erythematosus, because they respond to host DNA. Therefore, the regulation of PDC activation is critical for maintaining adequate immune responses. Here we show that an inhibitory major histocompatibility complex class I receptor, paired immunoglobulin-like receptor B (PIR-B), suppressed Fms-like tyrosine kinase 3 ligand-induced PDC differentiation in BM cells, as well as Toll-like receptor 9-mediated IFN-α production by PDCs, through the dephosphorylation of STAT1/STAT2. In particular, PIR-B inhibited IFN-α-mediated STAT phosphorylation, suggesting that PIR-B negatively regulates the positive feedback mechanism of IFN-α secretion triggered by Toll-like receptor 9. These results demonstrate a novel regulatory role for PIR-B in PDCs.
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Mitsuhashi
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
authors.forename: Shota
authors.initials: S
authors.lastname: Endo
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takeda
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yabe-Wada
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016898:Interferon-alpha / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*
chemical_list: D016898:Interferon-alpha; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C494080:Stat1 protein, mouse; C494085:Stat2 protein, mouse; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D051941:fms-Like Tyrosine Kinase 3