title: Alternatively activated dendritic cells derived from systemic lupus erythematosus patients have tolerogenic phenotype and function.
abstract: Tolerogenic dendritic cells (DCs) are potential cell-based therapy in autoimmune diseases. In this study, we generated alternatively activated DCs (aaDCs) by treating monocyte-derived DCs from patients with systemic lupus erythematosus (SLE) and healthy subjects with combination of 1,25 dihydroxyvitamin D(3) (vitD3) and dexamethasone followed by lipopolysaccharide-induced maturation. Lupus aaDCs were found to acquire semi-mature phenotype that remained maturation-resistant to immunostimulants. They produced low level of IL-12 but high level of IL-10. They had attenuated allostimulatory effects on T cell activation and proliferation comparable to normal aaDCs and demonstrated differential immunomodulatory effects on naïve and memory T cells. These aaDCs were capable of inducing IL-10 producing regulatory T effectors from naïve T cells whereas they modulated cytokine profile with suppressed production of IFN-γ and IL-17 by co-cultured memory T cells with attenuated proliferation. These aaDCs were shown to be superior to those generated using vitD3 alone in lupus patients.
authors.affiliation: Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Hong Kong, Hong Kong. Electronic address: chriswu1010@126.com.
authors.forename: Hai Jing
authors.initials: HJ
authors.lastname: Wu
authors.affiliation: Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Hong Kong, Hong Kong. Electronic address: yloa@hkucc.hku.hk.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lo
authors.affiliation: Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Hong Kong, Hong Kong. Electronic address: dlukmphil@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Luk
authors.affiliation: Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Hong Kong, Hong Kong. Electronic address: cslau@hku.hk.
authors.forename: Chak Sing
authors.initials: CS
authors.lastname: Lau
authors.affiliation: Department of Pathology, University of Hong Kong, Hong Kong. Electronic address: liweilu@hkucc.hku.hk.
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.affiliation: Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Hong Kong, Hong Kong. Electronic address: temy@hkucc.hku.hk.
authors.forename: Mo Yin
authors.initials: MY
authors.lastname: Mok
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014815:Vitamins / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D014815:Vitamins; D016753:Interleukin-10; D018664:Interleukin-12; D003907:Dexamethasone; D002117:Calcitriol
keywords: Dendritic cells;; Regulatory T cell;; Tolerogenicity;; Vitamin D3;