Molecular Cardiology, Whitaker Cardiovascular Institute, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA.
J Clin Immunol. 2011 Apr;31(2):167-73. doi: 10.1007/s10875-010-9486-2. Epub 2010 Nov 10.
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.
脂联素是一种脂肪细胞衍生的细胞因子，具有抗炎特性。矛盾的是，在许多炎症性疾病中，循环脂联素水平升高。因此，我们试图确定脂联素缺乏在自身免疫小鼠模型中的作用。在 C57BL/6 背景下缺乏脂联素的小鼠不会出现自身免疫表型。在允许的 MRL 背景下产生的缺乏脂联素的小鼠也未观察到自身免疫。然而，脂联素缺乏症加剧了 MRL-lpr 小鼠的自身免疫表型。与 MRL-lpr 小鼠相比，MRL-lpr.apn(-/-)小鼠表现出更大的淋巴结病和脾肿大，以及增加的抗核抗体和抗 dsDNA 产生。此外，对肾脏的评估显示，MRL-lpr.apn(-/-)小鼠的肾小球毛丛增大、新月形成、IgG 和 C3 沉积增加以及系膜扩张。脂联素缺乏对自身免疫表型的影响在雌性小鼠中比雄性小鼠更为明显。这些数据表明，尽管脂联素缺乏不足以引起自身免疫，但脂联素在狼疮的小鼠模型中作为自身免疫表型的负调节剂发挥作用。
