Modulation of lupus phenotype by adiponectin deficiency in autoimmune mouse models.
Adiponectin is an adipocyte-derived cytokine with anti-inflammatory properties. Paradoxically, circulating adiponectin levels are increased in a number of inflammatory diseases. Thus, we sought to define the role of adiponectin deficiency in mouse models of autoimmunity. Adiponectin-deficient mice on a C57BL/6 background do not develop an autoimmune phenotype. Autoimmunity was also not observed in adiponectin-deficient mice generated on the permissive MRL background. However, adiponectin deficiency exacerbated the autoimmune phenotype of MRL-lpr mice. Compared with MRL-lpr mice, MRL-lpr.apn(-/-) mice displayed greater lymphadenopathy and splenomegaly, as well as increased anti-nuclear antibody and anti-dsDNA production. In addition, evaluation of the kidney revealed larger glomerular tuft size, crescent formation, increased IgG and C3 deposits, and mesangial expansion in the MRL-lpr.apn(-/-) mice. The effects of adiponectin deficiency on the autoimmune phenotypes were more pronounced in female versus male mice. These data show that, while adiponectin deficiency is not sufficient to confer autoimmunity, adiponectin acts as a negative modulator of the autoimmune phenotype in a murine model of lupus.
Molecular Cardiology, Whitaker Cardiovascular Institute, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA.
Jennifer
J
Parker
Hanni
H
Menn-Josephy
Bari
B
Laskow
Yukihiro
Y
Takemura
Tamar
T
Aprahamian
D052242:Adiponectin / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D015551:Autoimmunity / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D056747:Immunomodulation; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008206:Lymphatic Diseases / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D010641:Phenotype; D013163:Splenomegaly / Q000473:pathology
D052242:Adiponectin; D000974:Antibodies, Antinuclear