title: Altered immunity and dendritic cell activity in the periphery of mice after long-term engraftment with bone marrow from ultraviolet-irradiated mice.
abstract: Alterations to dendritic cell (DC) progenitors in the bone marrow (BM) may contribute to long-lasting systemic immunosuppression (>28 d) following exposure of the skin of mice to erythemal UV radiation (UVR). DCs differentiated in vitro from the BM of mice 3 d after UVR (8 kJ/m(2)) have a reduced capacity to initiate immunity (both skin and airways) when adoptively transferred into naive mice. Studies in IL-10(-/-) mice suggested that UV-induced IL-10 was not significantly involved. To investigate the immune capabilities of peripheral tissue DCs generated in vivo from the BM of UV-irradiated mice, chimeric mice were established. Sixteen weeks after reconstitution, contact hypersensitivity responses were significantly reduced in mice reconstituted with BM from UV-irradiated mice (UV-chimeric). When the dorsal skin of UV-chimeric mice was challenged with innate inflammatory agents, the hypertrophy induced in the draining lymph nodes was minimal and significantly less than that measured in control-chimeric mice challenged with the same inflammatory agent. When DCs were differentiated from the BM of UV-chimeric mice using FLT3 ligand or GM-CSF + IL-4, the cells maintained a reduced priming ability. The diminished responses in UV-chimeric mice were not due to different numerical or proportional reconstitution of BM or the hematopoietic cells in blood, lymph nodes, and skin. Erythemal UVR may imprint a long-lasting epigenetic effect on DC progenitors in the BM and alter the function of their terminally differentiated progeny.
authors: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth 6008, Western Australia, Australia.
authors: Royce L X
authors: RL
authors: Ng
authors: Naomi M
authors: NM
authors: Scott
authors: Deborah H
authors: DH
authors: Strickland
authors: Shelley
authors: S
authors: Gorman
authors: Michele A
authors: MA
authors: Grimbaldeston
authors: Mary
authors: M
authors: Norval
authors: Jason
authors: J
authors: Waithman
authors: Prue H
authors: PH
authors: Hart
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D002465:Cell Movement / Q000276:immunology; D046528:Chimerism / Q000528:radiation effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects*; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006984:Hypertrophy; D007113:Immunity, Innate; D015847:Interleukin-4 / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor