1. Altered Immunity and Dendritic Cell Activity in the Periphery of Mice after Long-Term Engraftment with Bone Marrow from Ultraviolet-Irradiated Mice.
- Author
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Ng, Royce L. X., Scott, Naomi M., Strickland, Deborah H., Gorman, Shelley, Grimbaldeston, Michele A., Norval, Mary, Waithman, Jason, and Hart, Prue H.
- Subjects
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DENDRITIC cells , *BONE marrow , *IMMUNOSUPPRESSION , *PHYSIOLOGICAL effects of ultraviolet radiation , *GRANULOCYTE-macrophage colony-stimulating factor , *INTERLEUKIN-4 , *INTERLEUKIN-10 , *LABORATORY mice , *PHYSIOLOGY - 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/m²) 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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