UV-irradiation of skin alters haematopoirtic progenitors within the bone marrow and induces the differentiation of regulatory dendritic cells

[Truncated abstract] Exposure of humans and mice to ultraviolet radiation (UVR) can suppress systemic immune responses. However, the mechanism by which UVR modulates the immune system has not been clearly defined. In this study using mice, experiments are focused on dendritic cells (DCs) as they are key cells that link the innate and adaptive immune responses. We proposed that UV-irradiation of skin affects DC progenitors in the bone marrow (BM) and that DCs differentiating from the BM of UV-irradiated mice contribute to systemic immune suppression. When DCs were differentiated in vitro (using fms-like tyrosine kinase-3 or granulocyte macrophage colony-stimulating factor + interleukin-4) from the BM of UV-irradiated mice, they had a reduced ability to prime T cells when transferred into new mice. The UVR-induced effect on DC progenitors in the BM was rapid (observed within 1 d of UVR exposure) and long-lasting (detected 10 d after UVR exposure). The UVRinduced effect on DC progenitors within the BM was prevented by administration of indomethacin to mice prior to UV-irradiation. In addition, treatment with prostaglandin E2 was able to reproduce the effect of UV-irradiation on BM-derived DCs. Thus, UVRinduced prostaglandin E2 (and possibly other prostanoids) were responsible for the change in DC progenitors.