Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Kunming, China.
PLoS Biol. 2018 Aug 31;16(8):e2005354. doi: 10.1371/journal.pbio.2005354. eCollection 2018 Aug.
Leptin is a well-known adipokine that plays a critical role in immune responses. To further explore the immunological roles of leptin, we developed a transgenic leptin pig controlled by the pig leptin (pleptin) promoter to overexpress leptin. Symptoms typically associated with systemic lupus erythematosus (SLE) were evident in this transgenic pig strain, including anemia, leukopenia, and thrombocytopenia as well as kidney and liver impairment. Histologically, there were increased immunoglobulin G (IgG) levels, elevated antiplatelet antibody (APA) levels, and deposition of immune complexes in the kidney and liver. In addition, anti-double-stranded DNA antibodies (dsDNAs), antinuclear antibodies (ANAs), and antinucleosome antibodies (ANuAs) were all significantly increased in serum immunological examinations. These findings were also accompanied by repression of the regulatory T cell (Treg) ratio. Significantly, glucocorticoid experimental therapies partially relieved the autoimmune responses and bleeding symptoms observed in these transgenic leptin pigs. Together, these results indicate that leptin plays a critical role in the development of autoimmune disorders and demonstrate that our transgenic leptin pigs can act as a valuable model of SLE.
瘦素是一种众所周知的脂肪细胞因子，在免疫反应中起着关键作用。为了进一步探索瘦素的免疫学作用，我们开发了一种由猪瘦素（pleptin）启动子控制的过表达瘦素的转基因猪。这种转基因猪品系表现出与系统性红斑狼疮（SLE）相关的典型症状，包括贫血、白细胞减少和血小板减少以及肝肾功能损害。组织学上，免疫球蛋白 G（IgG）水平升高，抗血小板抗体（APA）水平升高，免疫复合物在肾脏和肝脏沉积。此外，血清免疫学检查中抗双链 DNA 抗体（dsDNAs）、抗核抗体（ANAs）和抗核小体抗体（ANuAs）均显著增加。这些发现还伴随着调节性 T 细胞（Treg）比例的抑制。值得注意的是，糖皮质激素实验治疗部分缓解了这些转基因瘦素猪中观察到的自身免疫反应和出血症状。综上所述，这些结果表明瘦素在自身免疫性疾病的发展中起着关键作用，并证明我们的转基因瘦素猪可以作为 SLE 的一个有价值的模型。
