Advertisement

NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells

Viviana Marzaioli, Margarita Hurtado-Nedelec, Coralie Pintard, Asma Tlili, Jean-Claude Marie, Renato C. Monteiro, Marie-Anne Gougerot-Pocidalo, Pham My-Chan Dang and Jamel El-Benna

Key Points

  • NOX5 and p22phox are both involved in Mo-DC differentiation.

  • In Mo-DC, NOX5 and p22phox create a complex on the outer membrane of the mitochondria.

Abstract

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.

  • Submitted October 18, 2016.
  • Accepted August 3, 2017.
View Full Text