title: DCIR negatively regulates CpG-ODN-induced IL-1β and IL-6 production.
abstract: C-type lectin receptors (CLR) are a diverse family of proteins mainly expressed on antigen-presenting cells (APC). As antigen-uptake and signaling receptors, CLR modulate immune responses of APC. The dendritic cell immunoreceptor (DCIR) is a member of CLR and has an immunoreceptor tyrosine based inhibitory motif (ITIM) in cytoplasmic tail, which is believed to play a negative role in cellular responses after antigen exposure. In addition to pathogen recognition, DCIR has been shown to be pivotal in preventing autoimmune disease by controlling dendritic cell proliferation. However, much less is known about the role of DCIR in innate immunity and its crosstalk with the Toll like receptors (TLR) pathway. In this study, we demonstrate that CpG-ODN stimulation can promote DCIR expression in macrophages and DCIR triggering inhibits the production of CpG-ODN-induced proinflammatory cytokines. We further confirm that siRNA-mediated knockdown of DCIR expression enhances CpG-ODN-induced phosphorylation of Erk1/2, JNK1/2 and p38 in macrophages. Collectively, these results indicate that DCIR is a negatively regulator in TLR9-mediated innate immune response.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xibao
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Junru
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: cwl@zju.edu.cn.
authors.forename: Weilin
authors.initials: W
authors.lastname: Chen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014162:Transfection
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; C526731:Dcir protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D037181:Lectins, C-Type; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9
keywords: C-type lectin receptors (CLR); Dendritic cell immunoreceptor (DCIR); Toll like receptors (TLR)