Symptoms of systemic lupus erythematosus are diagnosed in leptin transgenic pigs

Abstract

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.

Association of Leptin Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

“…Yousefian et al also revealed that leptin polymorphisms were related to the risk of MS and its clinical symptoms [ 43 ]. Most recently, Chen et al established a transgenic leptin pig overexpressing leptin and observed manifestations of SLE in this transgenic pig strain [ 44 ]. But a previous study of our group has not discovered the association between leptin polymorphisms with SLE in a Chinese population [ 45 ], which is consistent with previous studies [ 46 ].…”

“…Moreover, the function of the leptin gene in autoimmune diseases has received much attention in recent years [ 42 – 46 ]. It have been revealed that leptin plays a crucial role in the susceptibility to multiple sclerosis (MS) [ 42 , 43 ] and systemic lupus erythematosus (SLE) [ 44 ]. It also has been reported that leptin -deficient mice had decreased levels of TNF- α and IL-1 β , a less severe arthritis induced by antigen and defective cell-mediated immunity [ 47 ].…”

Endogenous leptin promotes autophagy in EBSS-induced PFCs

“…The WT and leptin transgenic PFCs were isolated and established from ear tissues of WT and leptin transgenic pigs (Chen et al 2018). The WT and leptin transgenic PFCs were cultured in basic (1×) Dulbecco’s modified Eagle’s medium (DMEM) (Gibco, NY, USA) supplemented with 10% fetal bovine serum (Ausbian, VS500 T) and 100 IU/ml penicillin.…”

Metabolic determinants of lupus pathogenesis

“…Transgenic expression of leptin in pigs results in a lupus-like disease characterized by increased anti-dsDNA antibodies, renal immune complex deposition, nephritis, and decreased frequency of Treg cells. 97 Leptin levels inversely correlate with the frequency of Treg cells in SLE patients. 83 Leptin deficiency in MRL/lpr lupus-prone mice was protective for disease development, and it increased the frequency of Treg cells.…”

“…Leptin signaling is necessary for murine Th17 effector functions, and it skews human and mouse T cells toward a Th1 phenotype in vitro, which is relevant to SLE patients who present an increased frequency of Th1 cells and IFNγ production. Transgenic expression of leptin in pigs results in a lupus‐like disease characterized by increased anti‐dsDNA antibodies, renal immune complex deposition, nephritis, and decreased frequency of Treg cells . Leptin levels inversely correlate with the frequency of Treg cells in SLE patients .…”