title: Inclusive estimation of complex antigen presentation functions of monocyte-derived dendritic cells differentiated under normoxia and hypoxia conditions.
abstract: Dendritic cells (DCs) generated from monocytes under 20% O2 are now used as therapeutic tools for cancer patients. However, the O2 concentration is between 3 and 0.5% in most tissues. We evaluated these complicated functions of DCs under oxygen tensions mimicking in vivo situations. Immature DCs (imDCs) were generated from monocytes using IL-4 and GM-CSF under normoxia (20% O2; N-imDCs) or hypoxia (1% O2; H-imDCs). Mature DCs (mDCs) were induced with LPS. DCs were further exposed to normoxia (N/N-DCs) or hypoxia (N/H-DCs and H/H-DCs) conditions. Using a 2-D culture system, H-DCs were smaller in size than N-DCs, and H/H-DCs exhibited higher allo-T cell stimulation ability than N/N-DCs and N/H-DCs. On the other hand, motility and phagocytic ability of H/H-DCs were significantly lower than those of N/H-DCs and N/N-DCs. In a 3-D culture system, however, maturation of H/H-imDCs and N/H-imDCs was suppressed compared with N/N-imDCs as a result of their decreased motility and phagocytosis. Interestingly, silencing of HIF-1α by RNA interference decreased CD83 expression without affecting any antigen presentation abilities except for the ability to stimulate the allo-T cell population. Our data could help our understanding of DCs, especially therapeutic DCs, in vivo.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Toshitatsu
authors.initials: T
authors.lastname: Ogino
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015151:Immunoblotting; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D010587:Phagocytosis / Q000276:immunology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007136:Immunoglobulins; D015847:Interleukin-4; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010100:Oxygen; D000097802:CD83 Antigen; C497442:HIF1A protein, human