| First Author | Huang X | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 11 | Pages | e112953 |
| PubMed ID | 25383620 | Mgi Jnum | J:225311 |
| Mgi Id | MGI:5692375 | Doi | 10.1371/journal.pone.0112953 |
| Citation | Huang X, et al. (2014) Peroxisome proliferator-activated receptor gamma deficiency in T cells accelerates chronic rejection by influencing the differentiation of CD4+ T cells and alternatively activated macrophages. PLoS One 9(11):e112953 |
| abstractText | BACKGROUND: In a previous study, activation of the peroxisome proliferator-activated receptor gamma (PPARgamma) inhibited chronic cardiac rejection. However, because of the complexity of chronic rejection and the fact that PPARgamma is widely expressed in immune cells, the mechanism of the PPARgamma-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 PPARgamma 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. PPARgamma-deficient regulatory T cells (Treg) were cocultured with monocytes to test their ability to induce alternatively activated macrophages (AAM). RESULTS: T cell-specific PPARgamma knockout recipients displayed reduced cardiac allograft survival and an increased degree of pathology compared with WT littermates. T cell-specific PPARgamma 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 PPARgamma deficiency in T cells through the action of Th2 and Treg. PPARgamma-deficient T cells eliminated the pioglitazone-induced polarization of AAM and reduced allograft survival. CONCLUSIONS: PPARgamma-deficient T cells influenced the T cell subset and AAM polarization in chronic allograft rejection. The mechanism of PPARgamma activation in transplantation tolerance could yield a novel treatment without side effects. |
