| First Author | Wei P | Year | 2023 |
| Journal | Commun Biol | Volume | 6 |
| Issue | 1 | Pages | 721 |
| PubMed ID | 37452099 | Mgi Jnum | J:352495 |
| Mgi Id | MGI:7510359 | Doi | 10.1038/s42003-023-05104-6 |
| Citation | Wei P, et al. (2023) Pparalpha knockout in mice increases the Th17 development by facilitating the IKKalpha/RORgammat and IKKalpha/Foxp3 complexes. Commun Biol 6(1):721 |
| abstractText | The helper CD4(+) T cell-type 17 (Th17) cells and regulatory CD4(+) T cells (Tregs) are balanced through numerous molecular regulators, particularly metabolic factors, and their alteration causes immune dysregulation. Herein, we report that peroxisome proliferator of activated receptor-alpha (Pparalpha), a lipid metabolism regulator, suppresses Th17 differentiation. We demonstrated that Pparalpha ablation improves Th17 and pro-Th17 factor HIF-1alpha by enhancing the expression and nuclear localization of NFkappaB-activator IkappaB kinase-alpha (IKKalpha). Unexpectedly, we found that IKKalpha directly interacts with RORgammat and enhances the expression of Il17a gene. Meanwhile, IKKalpha also interacts with Foxp3, leading to the post-translational regulation of Foxp3 by elevating its proteasomal degradation, and influencing Th17 development. Pparalpha deficiency leads to enhanced Th17 development in vivo and is associated with enhanced pathology in a murine experimental autoimmune encephalomyelitis (EAE) model. Overall, our data indicate that Pparalpha may serve as a potential therapeutic target for autoimmune and inflammatory diseases. |
