Oral Presentation 6th Australian Health and Medical Research Congress 2012

Ultraviolet irradiation of skin induces a long-lasting effect on dendritic cell precursors in bone marrow (#191)

Royce LX Ng 1 , Deborah H Strickland 1 , Naomi M Scott 1 , Shelley Gorman 1 , Jason C Waithman 1 , Prue H Hart 1
  1. Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Subiaco, WA, 6008, Australia
Exposure of C57BL/6 mice to UVR (8 kJ/m2) causes systemic immunosuppression that can last for over 4 weeks. We propose that UVR effects on dendritic cell precursors in the bone marrow are one mechanism of inducing long-lasting UVR-induced systemic immunosuppression. Dendritic cells cultured from the bone marrow of 3-day post-irradiated (8 kJ/m2) BALB/c mice have a reduced capacity to prime naïve T cells when adoptively transferred to naïve recipients. This UVR-induced effect was maintained when bone marrow cells were cultured in GM-CSF and IL-4, or FLT3L; culture conditions that produced dendritic cells with confirmed different phenotypes. To investigate the function of dendritic cells generated in vivo from the bone marrow of UV-irradiated mice, mouse chimeras were established. After 16 weeks, mice reconstituted with bone marrow from UV-irradiated mice (UV-chimeric) had a reduced contact hypersensitivity response compared to mice reconstituted with normal bone marrow (control-chimeric). In addition, when the dorsal skin of UV-chimeric mice were treated with either FITC or an erythemal dose of UVR (2 kJ/m2), there were reduced cell yields in the draining lymph nodes at 24 h. In FITC painted mice, the reduced cell yield corresponded with decreased FITC+ dendritic cells in the draining lymph nodes which were identified as migratory dermal dendritic cells. Furthermore, when the bone marrow of UV-chimeric mice was cultured for dendritic cell development, the cells had reduced priming ability. These reduced functional responses in UV-chimeric mice were not due to different numerical or proportional reconstitution of bone marrow or the leukocyte populations in secondary lymphoid organs when compared with control-chimeric mice. Our results suggest that UVR imprints a long-lasting effect on dendritic cell precursors in the bone marrow and reduces the function of the dendritic cells that are differentiated from these precursors. These findings demonstrate a mechanism not previously associated with UVR-induced systemic immunosuppression.