Eicosapentaenoic acid disrupts the balance between Tregs and IL-17+ T cells through PPARγ nuclear receptor activation and protects cardiac allografts

J Surg Res. 2012 Mar;173(1):161-70. doi: 10.1016/j.jss.2010.08.052. Epub 2010 Sep 27.


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 PPARγ was up-regulated. In mixed lymphocytes reaction (MLR), incubation with EPA significantly inhibited the proliferation of IL-17(+) T cells and promoted the proliferation of Tregs, while PPARγ 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 PPARγ nuclear receptor activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology
  • Animals
  • Cell Proliferation / drug effects
  • Eicosapentaenoic Acid / pharmacology*
  • Eicosapentaenoic Acid / therapeutic use*
  • Forkhead Transcription Factors / metabolism
  • Graft Rejection / physiopathology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Heart Transplantation / physiology*
  • Interleukin-17 / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Models, Animal
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / drug effects*
  • PPAR gamma / physiology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / pathology*
  • Transplantation, Homologous


  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • PPAR gamma
  • Eicosapentaenoic Acid