Remission of systemic lupus erythematosus disease activity with regulatory cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice
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AbstractThe 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 (T-reg) and IL-10(+) regulatory B (B-reg) 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-12R2) 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 T-reg and B-reg frequency in MRL/lpr mice with IL-35 treatment, compared to phosphate-buffered saline (PBS) treatment. mRNA expressions of T-reg-related FoxP3, IL-35 subunit (p35 and EBI3) and soluble IL-35 receptor subunit (gp130 and IL12R2) 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 T-reg-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.
All Author(s) ListCai Z, Wong CK, Dong J, Chu M, Jiao D, Kam NW, Lam CWK, Tam LS
Journal nameClinical and Experimental Immunology
Year2015
Month8
Day1
Volume Number181
Issue Number2
PublisherWiley: 12 months
Pages253 - 266
ISSN0009-9104
eISSN1365-2249
LanguagesEnglish-United Kingdom
Keywordscytokines; interleukin-35; regulatory B cells; regulatory T cells; systemic lupus erythematosus
Web of Science Subject CategoriesImmunology

Last updated on 2020-22-11 at 00:46