PMID- 28830888 OWN - NLM STAT- MEDLINE DCOM- 20171020 LR - 20210202 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 130 IP - 15 DP - 2017 Oct 12 TI - NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells. PG - 1734-1745 LID - 10.1182/blood-2016-10-746347 [doi] AB - 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 NFkappaB pathways. These data demonstrate that the NOX5-p22phox complex drives Mo-DC differentiation, and thus could be critical for immunity and inflammation. CI - (c) 2017 by The American Society of Hematology. FAU - Marzaioli, Viviana AU - Marzaioli V AUID- ORCID: 0000-0001-9410-0835 AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. FAU - Hurtado-Nedelec, Margarita AU - Hurtado-Nedelec M AUID- ORCID: 0000-0001-9681-7653 AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. AD - Departement d'Immunologie et d'Hematologie, UF Dysfonctionnements Immunitaires, Hopitaux Universitaires Paris Nord Val de Seine, Hopital Bichat, Paris, France. FAU - Pintard, Coralie AU - Pintard C AUID- ORCID: 0000-0002-2371-4968 AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. FAU - Tlili, Asma AU - Tlili A AUID- ORCID: 0000-0003-3963-6527 AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. FAU - Marie, Jean-Claude AU - Marie JC AUID- ORCID: 0000-0002-0559-638X AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. FAU - Monteiro, Renato C AU - Monteiro RC AUID- ORCID: 0000-0001-5202-5646 AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. AD - Departement d'Immunologie et d'Hematologie, UF Dysfonctionnements Immunitaires, Hopitaux Universitaires Paris Nord Val de Seine, Hopital Bichat, Paris, France. FAU - Gougerot-Pocidalo, Marie-Anne AU - Gougerot-Pocidalo MA AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. AD - Departement d'Immunologie et d'Hematologie, UF Dysfonctionnements Immunitaires, Hopitaux Universitaires Paris Nord Val de Seine, Hopital Bichat, Paris, France. FAU - Dang, Pham My-Chan AU - Dang PM AUID- ORCID: 0000-0002-7138-1037 AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. FAU - El-Benna, Jamel AU - El-Benna J AUID- ORCID: 0000-0001-5733-216X AD - INSERM-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France. AD - Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Departement Hospitalo Universitaire-Fibrosis Inflammation Remodeling, Faculte de Medecine, Site Xavier Bichat, Universite Paris Diderot, Paris, France; and. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170822 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Enzyme Inhibitors) RN - 0 (Free Radical Scavengers) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Proteins) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - EC 1.6.3.- (CYBB protein, human) RN - EC 1.6.3.- (NADPH Oxidase 2) RN - EC 1.6.3.- (NADPH Oxidase 5) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 1.6.3.- (NOX5 protein, human) RN - EC 1.6.3.1 (CYBA protein, human) SB - IM MH - *Cell Differentiation/drug effects MH - Dendritic Cells/*cytology/drug effects/metabolism MH - Enzyme Inhibitors/pharmacology MH - Free Radical Scavengers/pharmacology MH - Humans MH - Membrane Glycoproteins/metabolism MH - Membrane Proteins/antagonists & inhibitors/*metabolism MH - Mitochondria/drug effects/metabolism MH - Mitochondrial Membranes/drug effects/metabolism MH - Models, Biological MH - Monocytes/*cytology/drug effects/metabolism MH - NADPH Oxidase 2 MH - NADPH Oxidase 5 MH - NADPH Oxidases/antagonists & inhibitors/*metabolism MH - NF-kappa B/metabolism MH - Protein Binding/drug effects MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects EDAT- 2017/08/24 06:00 MHDA- 2017/10/21 06:00 CRDT- 2017/08/24 06:00 PHST- 2016/10/18 00:00 [received] PHST- 2017/08/03 00:00 [accepted] PHST- 2017/08/24 06:00 [pubmed] PHST- 2017/10/21 06:00 [medline] PHST- 2017/08/24 06:00 [entrez] AID - S0006-4971(20)32798-1 [pii] AID - 10.1182/blood-2016-10-746347 [doi] PST - ppublish SO - Blood. 2017 Oct 12;130(15):1734-1745. doi: 10.1182/blood-2016-10-746347. Epub 2017 Aug 22.