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Purified Eicosapentaenoic Acid Induces Prolonged Survival of Cardiac Allografts and Generates Regulatory T Cells
Author(s) -
Iwami D.,
Zhang Q.,
Aramaki O.,
omura K.,
Shirasugi N.,
Niimi M.
Publication year - 2009
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2009.02641.x
Subject(s) - eicosapentaenoic acid , foxp3 , medicine , splenocyte , transplantation , adoptive cell transfer , il 2 receptor , heart transplantation , andrology , immunology , pharmacology , endocrinology , polyunsaturated fatty acid , biology , t cell , biochemistry , spleen , fatty acid , immune system
Fish oil, which is rich in eicosapentaenoic acid (EPA), has been found to have immunomodulatory effects. We examined whether administration of purified EPA affected survival of fully mismatched murine cardiac allografts. Hearts from C57BL/10 (H‐2 b ) mice were transplanted into CBA (H‐2 k ) recipients treated with one intraperitoneal dose of purified EPA the day of transplantation. Untreated CBA recipients and recipients given 0.1 g/kg of EPA rejected C57BL/10 hearts (median survival time [MST], 8 and 13 days, respectively). With a 1.0 g/kg dose of EPA, graft survival was markedly prolonged (MST >100 days). To determine whether regulatory cells were generated, naïve mice (secondary recipients) underwent adoptive transfer of splenocytes from EPA‐treated primary recipients and cardiac allograft transplantation. Adoptive transfer of whole, CD4 + and CD4 + CD25 + splenocytes from EPA‐treated recipients induced indefinite survival in secondary recipients. Flow cytometry showed that the CD4 + CD25 + cells were Foxp3 + . In reverse transcriptase‐polymerase chain reaction (RT‐PCR) studies, the expression of peroxisome proliferator‐activated receptor γ (PPARγ) mRNA was upregulated by EPA treatment. A PPARγ antagonist abrogated the prolongation of graft survival induced by EPA treatment (MST, 13 days). Thus, in our model, purified EPA induced prolonged survival of fully mismatched cardiac allografts and generated regulatory T cells dependent on PPARγ activation.