Eicosapentaenoic Acid Disrupts the Balance Between Tregs and IL-17⁺ T?Cells Through PPAR¦Ã Nuclear Receptor Activation and Protects Cardiac Allografts

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• 作者：Ping Ye ; M.D.² ; Jun Li ; M.D.² ; Sihua Wang ; M.D. ; Aini Xie ; M.D. ; Wei Sun ; M.D. ; Jiahong Xia ; Ph.D. ; ^{profxjh@163.com}
• 关键词：eicosapentaenoic acid ; Tregs ; Th17 cell ; PPAR¦Ã ; cardiac transplantation
• 刊名：Journal of Surgical Research
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：173
• 期：1
• 页码：161-170
• 全文大小：1588 K

文摘

Eicosapentaenoic acid (EPA) is one of n-3 polyunsaturated fatty acids that possesses a wide array of anti-inflammatory effects but its effects, on transplantation in general and on Tregs and IL-17⁺ T cells in particular, are not well studied. We treated recipient mice of heart transplantation with EPA and examined the effect of EPA on the ratio of Tregs/IL-17⁺ T cells in an allogeneic heart transplant model. The hearts from BALB/c (H-2d) mice were transplanted into C57BL/6 (H-2b) mice, and the recipients were administered EPA (500 mg/kg/d, 250 mg/kg/d, or 100 mg/kg/d) from d 1 to 3 post-transplant. The survival of cardiac allografts in mice treated with EPA was significantly protracted. Further examination of donor hearts in EPA-treated group demonstrated that infiltrating Foxp3⁺ T cells were increased, IL-17⁺ T cells were decreased, and expression of PPAR¦Ã was up-regulated. In mixed lymphoctyes reaction (MLR), incubation with EPA significantly inhibited the proliferation of IL-17⁺ T cells and promoted the proliferation of Tregs, while PPAR¦Ã antagonists GW9662 could reverse the results. Our study demonstrated that EPA can effectively protect cardiac allografts and disrupt the balance between Tregs and IL-17⁺ T cells in a murine model. This effect is partially mediated by PPAR¦Ã nuclear receptor activation.