NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells.
Viviana MarzaioliMargarita Hurtado-NedelecCoralie PintardAsma TliliJean-Claude MarieRenato C MonteiroMarie-Anne Gougerot-PocidaloPham My-Chan DangJamel El BennaPublished in: Blood (2017)
Dendritic cells (DCs) are a heterogeneous population of professional antigen-presenting cells and are key cells of the immune system, acquiring different phenotypes in accordance with their localization during the immune response. A subset of inflammatory DCs is derived from circulating monocytes (Mo) and has a key role in inflammation and infection. The pathways controlling Mo-DC differentiation are not fully understood. Our objective was to investigate the possible role of nicotinamide adenine dinucleotide phosphate reduced form oxidases (NOXs) in Mo-DC differentiation. In this study, we revealed that Mo-DC differentiation was inhibited by NOX inhibitors and reactive oxygen species scavengers. We show that the Mo-DC differentiation was dependent on p22phox, and not on gp91phox/NOX2, as shown by the reduced Mo-DC differentiation observed in chronic granulomatous disease patients lacking p22phox. Moreover, we revealed that NOX5 expression was strongly increased during Mo-DC differentiation, but not during Mo-macrophage differentiation. NOX5 was expressed in circulating myeloid DC, and at a lower level in plasmacytoid DC. Interestingly, NOX5 was localized at the outer membrane of the mitochondria and interacted with p22phox in Mo-DC. Selective inhibitors and small interfering RNAs for NOX5 indicated that NOX5 controlled Mo-DC differentiation by regulating the JAK/STAT/MAPK and NFκB pathways. These data demonstrate that the NOX5-p22phox complex drives Mo-DC differentiation, and thus could be critical for immunity and inflammation.
Keyphrases
- dendritic cells
- reactive oxygen species
- immune response
- regulatory t cells
- oxidative stress
- induced apoptosis
- signaling pathway
- adipose tissue
- end stage renal disease
- endothelial cells
- acute myeloid leukemia
- rheumatoid arthritis
- single cell
- transcription factor
- inflammatory response
- chronic kidney disease
- artificial intelligence
- peritoneal dialysis
- idiopathic pulmonary fibrosis
- lps induced
- electronic health record
- patient reported outcomes
- data analysis
- pi k akt
- machine learning