title: Influence of hypoxia-inducible factor 1α on dendritic cell differentiation and migration.
abstract: Dendritic cells(DCs) are important sentinels of the immune system and frequently reside in areas of low oxygen availability, in particular in the course of inflammatory processes. Hypoxia-inducible transcription factor (HIF)1α is responsible for major alterations in gene expression as part of the cellular adaptation to low oxygen concentration. In this study, we generated mice with a conditional deletion of HIF1α in DCs. Bone marrow-derived DCs from WT and conditional mutant mice expressed elevated levels of major histocompatibility complex class II and CD86 when grown in a hypoxic environment, whereas production of the cytokines interleukin (IL)-12p70, IL-10, IL-6, TNF-α, IL-1β, and IL-23 was reduced, both independent of HIF1α expression. In contrast, secretion of IL-22 was strongly enhanced under hypoxic conditions in an HIF1α-dependent manner. The chemokine receptor CCR7 was expressed at higher levels in wild-type DCs compared with HIF1α-deficient DCs, whereas the production of CCL17 and CCL22 was increased in conditions of low oxygen. Using in vitro as well as in vivo migration assays, we observed an enhanced migratory capability of DCs generated under hypoxia, which was HIF1α-dependent. Taken together, our data indicate that HIF1α plays an important role for DC differentiation and migration in a low oxygen environment.
authors.affiliation: Molecular Immunology, IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Köhler
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Randall S
authors.initials: RS
authors.lastname: Johnson
authors.forename: Heike
authors.initials: H
authors.lastname: Weighardt
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D015687:Cell Hypoxia / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000276:immunology
chemical_list: D051940:B7-2 Antigen; C515371:Ccr7 protein, mouse; C497965:Cd86 protein, mouse; D016207:Cytokines; C497443:Hif1a protein, mouse; D000949:Histocompatibility Antigens Class II; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D054400:Receptors, CCR7