| First Author | Tian D | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 2 | Pages | 3367-3378 |
| PubMed ID | 31919912 | Mgi Jnum | J:296777 |
| Mgi Id | MGI:6469799 | Doi | 10.1096/fj.201902069R |
| Citation | Tian D, et al. (2020) Deletion of Ppard in CD11c(+) cells attenuates atherosclerosis in ApoE knockout mice. FASEB J 34(2):3367-3378 |
| abstractText | Pparddelta, one of the lipid-activated nuclear receptor expressed in many cell types to activate gene transcription, also regulates cellular functions other than lipid metabolism. The mechanism regulating the function of antigen-presenting cells during the development of atherosclerosis is not fully understood. Here we aimed to study the involvement of PPARdelta in CD11c(+) cells in atherosclerosis. We used the Cre-loxP approach to make conditional deletion of Ppard in CD11c(+) cells in mice on Apoe(-/-) background, which were fed with high cholesterol diet to develop atherosclerosis. Ppard deficiency in CD11c(+) cells attenuated atherosclerotic plaque formation and infiltration of myeloid-derived dendritic cells (DCs) and T lymphocytes. Reduced lesion was accompanied by reduced activation of dendritic cells, and also a reduction of activation and differentiation of T cells to Th1 cells. In addition, DC migration to lymph node was also attenuated with Ppard deletion. In bone marrow-derived DCs, Ppard deficiency reduced palmitic acid-induced upregulation of co-stimulatory molecules and pro-inflammatory cytokine IL12 and TNFalpha. Our results indicated PPARdelta activation by fatty acid resulted in the activation of myeloid DCs and subsequent polarization of T lymphocytes, which contributed to atherosclerosis in Apoe(-/-) mice. These findings also reveal the potential regulatory role of PPARdelta in antigen presentation to orchestrate the immune responses during atherosclerosis. |
