IL-10 regulates murine lupus

Zhinan Yin, Gul Bahtiyar, Na Zhang, Lanzhen Liu, Ping Zhu, Marie E. Robert, Jennifer McNiff, Michael P. Madaio, Joe Craft

Research output: Contribution to journalArticle

177 Scopus citations

Abstract

MRL/MpJ-Tnfrsf6lpr (MRL/MpJ-Faslpr; MRL-Faslpr) mice develop a spontaneous lupus syndrome closely resembling human systemic lupus erythematosus. To define the role of IL-10 in the regulation of murine lupus, IL-10 gene-deficient (IL-10-/-) MRL-Faslpr (MRL-Faslpr IL-10-/-) mice were generated and their disease phenotype was compared with littermates with one or two copies of an intact IL-10 locus (MRL-Faslpr IL-10+/- and MRL-Faslpr IL-10+/+ mice, respectively). MRL-Faslpr IL-10-/- mice developed severe lupus, with earlier appearance of skin lesions, increased lymphadenopathy, more severe glomerulonephritis, and higher mortality than their IL-10-intact littermate controls. The increased severity of lupus in MRL-Faslpr IL-10-/- mice was closely associated with enhanced IFN-γ production by both CD4+ and CD8+ cells and increased serum concentration of IgG2a anti-dsDNA autoantibodies. The protective effect of IL-10 in this lupus model was further supported by the observation that administration of rIL-10 reduced IgG2a anti-dsDNA autoantibody production in wild-type MRL-Faslpr animals. In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus.

Original languageEnglish (US)
Pages (from-to)2148-2155
Number of pages8
JournalJournal of Immunology
Volume169
Issue number4
DOIs
StatePublished - Aug 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yin, Z., Bahtiyar, G., Zhang, N., Liu, L., Zhu, P., Robert, M. E., McNiff, J., Madaio, M. P., & Craft, J. (2002). IL-10 regulates murine lupus. Journal of Immunology, 169(4), 2148-2155. https://doi.org/10.4049/jimmunol.169.4.2148