| First Author | Tran CW | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 12 | Pages | e0244366 |
| PubMed ID | 33382742 | Mgi Jnum | J:299514 |
| Mgi Id | MGI:6500800 | Doi | 10.1371/journal.pone.0244366 |
| Citation | Tran CW, et al. (2020) Hypoxia-inducible factor 1 alpha limits dendritic cell stimulation of CD8 T cell immunity. PLoS One 15(12):e0244366 |
| abstractText | Dendritic cells are sentinels of the immune system and represent a key cell in the activation of the adaptive immune response. Hypoxia-inducible factor 1 alpha (HIF-1alpha)-a crucial oxygen sensor stabilized during hypoxic conditions-has been shown to have both activating and inhibitory effects in immune cells in a context- and cell-dependent manner. Previous studies have demonstrated that in some immune cell types, HIF-1alpha serves a pro-inflammatory role. Genetic deletion of HIF-1alpha in macrophages has been reported to reduce their pro-inflammatory function. In contrast, loss of HIF-1alpha enhanced the pro-inflammatory activity of dendritic cells in a bacterial infection model. In this study, we aimed to further clarify the effects of HIF-1alpha in dendritic cells. Constitutive expression of HIF-1alpha resulted in diminished immunostimulatory capacity of dendritic cells in vivo, while conditional deletion of HIF-1alpha in dendritic cells enhanced their ability to induce a cytotoxic T cell response. HIF-1alpha-expressing dendritic cells demonstrated increased production of inhibitory mediators including IL-10, iNOS and VEGF, which correlated with their reduced capacity to drive effector CD8+ T cell function. Altogether, these data reveal that HIF-1alpha can promote the anti-inflammatory functions of dendritic cells and provides insight into dysfunctional immune responses in the context of HIF-1alpha activation. |
