Authors:
Ng RLX, Scott NM, Strickland DH, Gorman S, Grimbaldeston MA, Norval M, Waithman J, Hart PH
Authors notes:
Journal of Immunology. 2013;190(11):5471-5484
Keywords:
Dendritic cell, bone marrow, UV radiation, inflammatory response, epigenetic, dendritic cell progenitors
Abstract:
Alterations to dendritic cell (DC) progenitors in the bone marrow (BM) may contribute to long-lasting systemic immunosuppression 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 controlchimeric 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.