Hypoxia-inducible factor 1 alpha limits dendritic cell stimulation of CD8 T cell immunity.

Autor: Tran CW; Princess Margaret Cancer Centre, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Gold MJ; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Garcia-Batres C; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Tai K; Princess Margaret Cancer Centre, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Elford AR; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Himmel ME; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Elia AJ; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Ohashi PS; Princess Margaret Cancer Centre, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Dec 31; Vol. 15 (12), pp. e0244366. Date of Electronic Publication: 2020 Dec 31 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0244366
Abstrakt: 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-1α)-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-1α serves a pro-inflammatory role. Genetic deletion of HIF-1α in macrophages has been reported to reduce their pro-inflammatory function. In contrast, loss of HIF-1α 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-1α in dendritic cells. Constitutive expression of HIF-1α resulted in diminished immunostimulatory capacity of dendritic cells in vivo, while conditional deletion of HIF-1α in dendritic cells enhanced their ability to induce a cytotoxic T cell response. HIF-1α-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-1α can promote the anti-inflammatory functions of dendritic cells and provides insight into dysfunctional immune responses in the context of HIF-1α activation.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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