title: Remission of systemic lupus erythematosus disease activity with regulatory cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice.
abstract: The immunological mechanisms mediated by regulatory cytokine interleukin (IL)-35 are unclear in systemic lupus erythematosus (SLE). We investigated the frequency of CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) regulatory T (Treg ) and IL-10(+) regulatory B (Breg ) cells and related immunoregulatory mechanisms in a female Murphy Roths Large (MRL)/lpr mouse model of spontaneous lupus-like disease, with or without IL-35 treatment. A remission of histopathology characteristics of lupus flare and nephritis was observed in the MRL/lpr mice upon IL-35 treatment. Accordingly, IL-35 and IL-35 receptor subunits (gp130 and IL-12Rβ2) and cytokines of MRL/lpr and BALB/c mice (normal controls) were measured. The increased anti-inflammatory cytokines and decreased proinflammatory cytokines were possibly associated with the restoration of Treg and Breg frequency in MRL/lpr mice with IL-35 treatment, compared to phosphate-buffered saline (PBS) treatment. mRNA expressions of Treg -related FoxP3, IL-35 subunit (p35 and EBI3) and soluble IL-35 receptor subunit (gp130 and IL12Rβ2) in splenic cells were up-regulated significantly in IL-35-treated mice. Compared with the PBS treatment group, IL-35-treated MRL/lpr mice showed an up-regulation of Treg -related genes and the activation of IL-35-related intracellular Janus kinase/signal transducer and activator of transcription signal pathways, thereby indicating the immunoregulatory role of IL-35 in SLE. These in vivo findings may provide a biochemical basis for further investigation of the regulatory mechanisms of IL-35 for the treatment of autoimmune-mediated inflammation.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.|Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong.
authors.forename: C K
authors.initials: CK
authors.lastname: Wong
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: M
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: D
authors.initials: D
authors.lastname: Jiao
authors.affiliation: Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.|Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: N W
authors.initials: NW
authors.lastname: Kam
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau.
authors.forename: C W K
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.|Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: L S
authors.initials: LS
authors.lastname: Tam
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000276:immunology; D012074:Remission Induction; D050791:STAT Transcription Factors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; C508443:Il12rb2 protein, mouse; D007378:Interleukins; D021122:Protein Subunits; D012333:RNA, Messenger; D053707:Receptors, Interleukin-12; D050791:STAT Transcription Factors; C569375:interleukin-35, mouse; D016753:Interleukin-10; D050822:Cytokine Receptor gp130; D053613:Janus Kinase 1
keywords: cytokines; interleukin-35; regulatory B cells; regulatory T cells; systemic lupus erythematosus
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