title: Characterization of regulatory dendritic cells differentiated from the bone marrow of UV-irradiated mice.
abstract: When antigen-loaded dendritic cells (DCs) differentiated from the bone marrow (BM) of UV-irradiated mice (UV-BMDCs) were adoptively transferred into naive mice or mice pre-sensitized with that antigen, the recipients exhibited a reduced immune response following antigen challenge. Hence, UV-BMDCs are poorly immunogenic and can suppress pre-existing immunity. The UV-induced effect on BM-derived DCs was rapid (observed 1 day after UV radiation), long-lasting (observed 10 days after UV radiation) and UV dose-dependent. The mechanism by which UV-BMDCs could regulate immunity was investigated. The CD11c(+) cells, differentiated using granulocyte-macrophage colony-stimulating factor + interleukin-4, were confirmed to be DCs because they did not express the myeloid-derived suppressor cell marker, Gr1. UV-BMDCs did not display altered antigen uptake, processing or ability to activate T cells in vitro. When gene expression in UV-BMDCs and DCs differentiated from the BM of non-irradiated mice (control-BMDCs) was examined, Ccl7, Ccl8 and CSF1R (CD115) mRNA transcripts were up-regulated in UV-BMDCs compared with control-BMDCs. However, neutralizing antibodies for Ccl7 and Ccl8 did not abrogate the reduced immunogenicity of UV-BMDCs in vivo. Moreover, the up-regulation of CSF1R transcript did not correspond with increased receptor expression on UV-BMDCs. The phenotypes of UV-BMDCs and control-BMDCs were similar, with no difference in the expression of CD4, CD8α, CD103, B220 or F4/80, or the regulatory molecules CCR7 (CD197), FasL (CD95L), B7H3 (CD276) and B7H4. However, PDL1 (CD274) expression was reduced in UV-BMDCs compared with control-BMDCs following lipopolysaccharide stimulation. In summary, UV-BMDCs do not express the classical phenotypic or gene expression properties of DCs reported by others as 'regulatory' or 'tolerogenic'.
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, WA, Australia.
authors.forename: Royce L X
authors.initials: RL
authors.lastname: Ng
authors.forename: Naomi M
authors.initials: NM
authors.lastname: Scott
authors.forename: Jackie L
authors.initials: JL
authors.lastname: Bisley
authors.forename: Misty J
authors.initials: MJ
authors.lastname: Lambert
authors.forename: Shelley
authors.initials: S
authors.lastname: Gorman
authors.forename: Mary
authors.initials: M
authors.lastname: Norval
authors.forename: Prue H
authors.initials: PH
authors.lastname: Hart
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D002478:Cells, Cultured; D054410:Chemokine CCL7 / Q000235:genetics / Q000378:metabolism; D054412:Chemokine CCL8 / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects; D019672:Genes, T-Cell Receptor; D007108:Immune Tolerance / Q000187:drug effects / Q000528:radiation effects*; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; D039521:CD11c Antigen; C515451:Ccl7 protein, mouse; C515454:Ccl8 protein, mouse; C498919:Cd274 protein, mouse; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016186:Receptor, Macrophage Colony-Stimulating Factor; D007213:Indomethacin
keywords: bone marrow; dendritic cell; regulation; ultraviolet radiation