title: MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice.
abstract: Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by hyperactivated immune responses to self-antigens and persistent systemic inflammation. Previously, we reported abnormalities in circulating and bone marrow (BM)-derived plasmacytoid dendritic cells (pDCs) from SLE patients. Here, we aim to seek for potential regulators that mediate functional aberrations of pDCs in SLE. BM-derived pDCs from NZB/W F1 mice before and after the disease onset were compared for toll-like receptor (TLR) induced responses and microRNA profile changes. While pDCs derived from symptomatic mice were phenotypically comparable to pre-symptomatic ones, functionally they exhibited hypersensitivity to TLR7 but not TLR9 stimulation, as represented by the elevated upregulation of CD40, CD86 and MHC class II molecules upon R837 stimulation. Upregulated induction of miR-155 in symptomatic pDCs following TLR7 stimulation was observed. Transfection of miR-155 mimics in pre-symptomatic pDCs induced an augmented expression of Cd40, which is consistent with the increased CD40 expression in symptomatic pDCs. Overall, our results provide evidence for miR-155-mediated regulation in pDC functional abnormalities in SLE. Findings from this study contribute to a better understanding of SLE pathogenesis and ignite future interests in evaluating the molecular regulation in autoimmunity.
authors: Departments of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. ssyan@hku.hk.|School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. ssyan@hku.hk.
authors: Sheng
authors: S
authors: Yan
authors: Departments of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. adayim@connect.hku.hk.
authors: Lok Yan
authors: LY
authors: Yim
authors: Departments of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. rach0806@connect.hku.hk.
authors: Rachel Chun Yee
authors: RC
authors: Tam
authors: Departments of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. wkchanf@hku.hk.
authors: Albert
authors: A
authors: Chan
authors: Departments of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. liweilu@hkucc.hku.hk.
authors: Liwei
authors: L
authors: Lu
authors: Departments of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. sfvchan@hku.hk.
authors: Chak Sing
authors: CS
authors: Lau
authors: Departments of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. cslau@hku.hk.
authors: Vera Sau-Fong
authors: VS
authors: Chan
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D034622:RNA Interference; D051199:Toll-Like Receptor 7 / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7
keywords: microRNAs; plasmacytoid dendritic cells; systemic lupus erythematosus; toll-like receptor 7