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-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.
AB - 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.
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U2 - 10.4049/jimmunol.169.4.2148
DO - 10.4049/jimmunol.169.4.2148
M3 - Article
C2 - 12165544
AN - SCOPUS:0037103150
SN - 0022-1767
VL - 169
SP - 2148
EP - 2155
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -