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

173 Citations (Scopus)

Abstract

MRL/MpJ-Tnfrsf6 lpr (MRL/MpJ-Fas lpr ; MRL-Fas lpr ) 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-Fas lpr (MRL-Fas lpr 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-Fas lpr IL-10 +/- and MRL-Fas lpr IL-10 +/+ mice, respectively). MRL-Fas lpr 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-Fas lpr 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-Fas lpr 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

Fingerprint

Interleukin-10
Autoantibodies
Genes
Inbred MRL lpr Mouse
Glomerulonephritis
Systemic Lupus Erythematosus
Cytokines
Phenotype
Skin
Mortality

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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

IL-10 regulates murine lupus. / Yin, Zhinan; Bahtiyar, Gul; Zhang, Na; Liu, Lanzhen; Zhu, Ping; Robert, Marie E.; McNiff, Jennifer; Madaio, Michael P.; Craft, Joe.

In: Journal of Immunology, Vol. 169, No. 4, 15.08.2002, p. 2148-2155.

Research output: Contribution to journalArticle

Yin, Z, Bahtiyar, G, Zhang, N, Liu, L, Zhu, P, Robert, ME, McNiff, J, Madaio, MP & Craft, J 2002, 'IL-10 regulates murine lupus', Journal of Immunology, vol. 169, no. 4, pp. 2148-2155. https://doi.org/10.4049/jimmunol.169.4.2148
Yin Z, Bahtiyar G, Zhang N, Liu L, Zhu P, Robert ME et al. IL-10 regulates murine lupus. Journal of Immunology. 2002 Aug 15;169(4):2148-2155. https://doi.org/10.4049/jimmunol.169.4.2148
Yin, Zhinan ; Bahtiyar, Gul ; Zhang, Na ; Liu, Lanzhen ; Zhu, Ping ; Robert, Marie E. ; McNiff, Jennifer ; Madaio, Michael P. ; Craft, Joe. / IL-10 regulates murine lupus. In: Journal of Immunology. 2002 ; Vol. 169, No. 4. pp. 2148-2155.
@article{21d0aa7c67994285a573bf1724b3c756,
title = "IL-10 regulates murine lupus",
abstract = "MRL/MpJ-Tnfrsf6 lpr (MRL/MpJ-Fas lpr ; MRL-Fas lpr ) 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-Fas lpr (MRL-Fas lpr 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-Fas lpr IL-10 +/- and MRL-Fas lpr IL-10 +/+ mice, respectively). MRL-Fas lpr 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-Fas lpr 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-Fas lpr 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.",
author = "Zhinan Yin and Gul Bahtiyar and Na Zhang and Lanzhen Liu and Ping Zhu and Robert, {Marie E.} and Jennifer McNiff and Madaio, {Michael P.} and Joe Craft",
year = "2002",
month = "8",
day = "15",
doi = "10.4049/jimmunol.169.4.2148",
language = "English (US)",
volume = "169",
pages = "2148--2155",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - IL-10 regulates murine lupus

AU - Yin, Zhinan

AU - Bahtiyar, Gul

AU - Zhang, Na

AU - Liu, Lanzhen

AU - Zhu, Ping

AU - Robert, Marie E.

AU - McNiff, Jennifer

AU - Madaio, Michael P.

AU - Craft, Joe

PY - 2002/8/15

Y1 - 2002/8/15

N2 - MRL/MpJ-Tnfrsf6 lpr (MRL/MpJ-Fas lpr ; MRL-Fas lpr ) 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-Fas lpr (MRL-Fas lpr 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-Fas lpr IL-10 +/- and MRL-Fas lpr IL-10 +/+ mice, respectively). MRL-Fas lpr 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-Fas lpr 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-Fas lpr 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.

AB - MRL/MpJ-Tnfrsf6 lpr (MRL/MpJ-Fas lpr ; MRL-Fas lpr ) 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-Fas lpr (MRL-Fas lpr 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-Fas lpr IL-10 +/- and MRL-Fas lpr IL-10 +/+ mice, respectively). MRL-Fas lpr 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-Fas lpr 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-Fas lpr 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.

UR - http://www.scopus.com/inward/record.url?scp=0037103150&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037103150&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.169.4.2148

DO - 10.4049/jimmunol.169.4.2148

M3 - Article

C2 - 12165544

AN - SCOPUS:0037103150

VL - 169

SP - 2148

EP - 2155

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -