Deficient Leptin Signaling Ameliorates Systemic Lupus Erythematosus Lesions in MRL/Mp-Faslpr Mice
Deficient Leptin Signaling Ameliorates Systemic Lupus Erythematosus Lesions in MRL/Mp-Faslpr Mice
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DOI：
10.4049/jimmunol.1301685
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发表时间：
2014-02-01
影响因子：
4.4
通讯作者：
Umehara, Hisanori
中科院分区：
文献类型：
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作者：
Fujita, Yoshimasa;Fujii, Takao;Umehara, Hisanori
瘦素由脂肪细胞、胎盘和胃分泌。它不仅通过下丘脑中的瘦素受体控制食欲，还调节免疫力。在目前的研究中，我们建立了瘦素缺乏的MRL/MP-Fas(LPR)小鼠，以探讨瘦素在自身免疫中的潜在作用。将C57BL/6J-ob/ob小鼠与人系统性红斑狼疮(SLE)样病变的MRL/MP-Fas(LPR)小鼠回交。研究瘦素缺乏对MRL/MP-Fas(LPR)小鼠各种类SLE表现的影响。用流式细胞仪分析脾组织中调节性T细胞的数量，并在体外观察瘦素对调节性T细胞和Th17细胞的影响。与瘦素产生的MRL/MP-Fas(LPR)小鼠相比，瘦素缺乏的MRL/MP-Fas(LPR)小鼠的脾肿大程度较小，CD3(+)、CD4(-)、CD8(-)、B220(+)T细胞(LPR细胞)的数量特别少。小鼠血清抗dsDNA抗体浓度较低，20wk时肾脏组织学改变明显减轻。瘦素缺陷型MRL/MP-Fas(LPR)小鼠脾内调节性T细胞增多。瘦素在体外抑制调节性T细胞和增强Th17细胞。综上所述，阻断瘦素信号可能对SLE和其他自身免疫性疾病患者有治疗作用。
Leptin is secreted by adipocytes, the placenta, and the stomach. It not only controls appetite through leptin receptors in the hypothalamus, it also regulates immunity. In the current study, we produced leptin-deficient MRL/Mp-Fas(lpr) mice to investigate the potential role of leptin in autoimmunity. C57BL/6J-ob/ob mice were backcrossed with MRL/Mp-Fas(lpr) mice, which develop human systemic lupus erythematosus (SLE)-like lesions. The effects of leptin deficiency on various SLE-like manifestations were investigated in MRL/Mp-Fas(lpr) mice. The regulatory T cell population in the spleen was analyzed by flow cytometry, and the effects of leptin on regulatory T cells and Th17 cells were evaluated in vitro. Compared with leptin-producing MRL/Mp-Fas(lpr) mice, leptindeficient MRL/Mp-Fas(lpr) mice showed less marked splenomegaly and a particularly low population of CD3(+)CD4(-)CD8(-)B220(+) T cells (lpr cells). Their serum concentrations of Abs to dsDNA were lower, and renal histological changes at age 20 wk were ameliorated. Regulatory T cells were increased in the spleens of leptin-deficient MRL/Mp-Fas(lpr) mice. Leptin suppressed regulatory T cells and enhanced Th17 cells in vitro. In conclusion, blockade of leptin signaling may be of therapeutic benefit in patients with SLE and other autoimmune diseases.