期刊
PLOS BIOLOGY
卷 16, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.2005354
关键词
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资金
- National Natural Science Key Foundation of China [81430075]
- National Natural Science Foundation of China Distinguished Young Scholar award [81225013]
- National Natural Science Foundation of China [81572677, 31560637]
- National Genetically Modified Organisms Breeding Major Projects [2016ZX08009-003-006]
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, antidouble-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.
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