Ontology highlight
ABSTRACT: Background
In a previous study, activation of the peroxisome proliferator-activated receptor ? (PPAR?) inhibited chronic cardiac rejection. However, because of the complexity of chronic rejection and the fact that PPAR? is widely expressed in immune cells, the mechanism of the PPAR?-induced protective effect was unclear.Materials and methods
A chronic rejection model was established using B6.C-H-2bm12KhEg (H-2bm12) mice as donors, and MHC II-mismatched T-cell-specific PPAR? knockout mice or wild type (WT) littermates as recipients. The allograft lesion was assessed by histology and immunohistochemistry. T cells infiltrates in the allograft were isolated, and cytokines and subpopulations were detected using cytokine arrays and flow cytometry. Transcription levels in the allograft were measured by RT-PCR. In vitro, the T cell subset differentiation was investigated after culture in various polarizing conditions. PPAR?-deficient regulatory T cells (Treg) were cocultured with monocytes to test their ability to induce alternatively activated macrophages (AAM).Results
T cell-specific PPAR? knockout recipients displayed reduced cardiac allograft survival and an increased degree of pathology compared with WT littermates. T cell-specific PPAR? knockout resulted in more CD4+ T cells infiltrating into the allograft and altered the Th1/Th2 and Th17/Treg ratios. The polarization of AAM was also reduced by PPAR? deficiency in T cells through the action of Th2 and Treg. PPAR?-deficient T cells eliminated the pioglitazone-induced polarization of AAM and reduced allograft survival.Conclusions
PPAR?-deficient T cells influenced the T cell subset and AAM polarization in chronic allograft rejection. The mechanism of PPAR? activation in transplantation tolerance could yield a novel treatment without side effects.
SUBMITTER: Huang X
PROVIDER: S-EPMC4226585 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
PloS one 20141110 11
<h4>Background</h4>In a previous study, activation of the peroxisome proliferator-activated receptor γ (PPARγ) inhibited chronic cardiac rejection. However, because of the complexity of chronic rejection and the fact that PPARγ is widely expressed in immune cells, the mechanism of the PPARγ-induced protective effect was unclear.<h4>Materials and methods</h4>A chronic rejection model was established using B6.C-H-2bm12KhEg (H-2bm12) mice as donors, and MHC II-mismatched T-cell-specific PPARγ knock ...[more]