Ultraviolet Irradiation of Mice Reduces the Competency of Bone Marrow-Derived CD11c+ Cells via an Indomethacin-Inhibitable Pathway

Abstract

Direct UV irradiation of dendritic cells and Langerhans cells reduces their Ag presenting ability. However, the effects of UV on CD11c+ cells located distally to the point of irradiation are poorly understood. Three days after UV irradiation (8 kJ/m2) of BALB/c mice, bone marrow cells were isolated and cultured for 7 d with IL-4 and GM-CSF for the propagation of CD11c+ cells. Bone marrow-derived CD11c+ cells from UV-irradiated or nonirradiated mice were loaded with dinitrobenzene sulfonic acid and injected into the ear pinnas of naive BALB/c mice. After 7 d, the ears were painted with 2,4-dinitro-1-fluorobenzene and the ear swelling determined 24 h later. A reduced contact hypersensitivity response was found in mice injected with CD11c+ cells from the UV-irradiated animals compared with those injected with cells from the nonirradiated animals. Further, a long-lasting suppression of the memory response to 2,4-dinitro-1-fluorobenzene was created. This suppressed response corresponded to increased IL-10 and PGE2 secretion by freshly isolated bone marrow cells from UV-irradiated mice, and to increased myelopoiesis. The reduction in competence of bone marrow-derived CD11c+ cells from UV-irradiated mice was not due to delayed maturation, as it was maintained upon LPS exposure prior to CD11c+ cell purification. The UV-induced effect was reversed by the administration of indomethacin to mice prior to UV irradiation and could be reproduced by s.c. PGE2. These results show that UV irradiation of mice can affect the function of bone marrow-derived CD11c+ cells via a mechanism inhibitable by indomethacin; this pathway is likely to contribute to systemic UV-induced immunosuppression.

Altered Immunity and Dendritic Cell Activity in the Periphery of Mice after Long-Term Engraftment with Bone Marrow from Ultraviolet-Irradiated Mice

“…Our previous studies using BM cells in culture suggested that UVR altered DC progenitors in the BM such that the differentiated DCs had reduced priming ability (17). We now confirm using chimeric mice that an erythemal dose of UVR delivered to shaved dorsal skin modulates DC progenitors within the BM and that this effect is long-lasting.…”

“…1A). As performed previously, BM was obtained 3 d post-UVR exposure (17). After 9 d, the cells were pulsed with DNBS (1 mM), and 10 6 cells were injected into the ear pinnae of naive mice.…”

“…Our previous results describing poorly immunogenic DCs differentiated from the BM of UV-irradiated BALB/c mice were obtained using GM-CSF + IL-4 as the differentiative growth factors (17). To test whether UV irradiation of mice alters BM-derived DCs generated in steady-state culture conditions, the BM cells of UV-irradiated BALB/c mice were cultured with FLT3-L for 9 d (Fig.…”

“…We reported previously that DCs differentiated in vitro from the BM of UV-irradiated BALB/c mice, and then transferred into naive recipients, have reduced priming ability as determined using an Agspecific recall response (17). This suggests that signals from UVirradiated skin alter the hematopoietic cell compartment such that, upon differentiation, BM-derived DCs have reduced priming ability.…”

“…Adoptive transfer of DCs differentiated from BM into naive recipients for an in vivo priming assay Cells were prepared and transferred into naive recipients as previously described (17). Briefly, BM cells cultured for 7 d (in GM-CSF + IL-4) were enriched to .95% CD11c + cells (confirmed by flow cytometry) using magnetic beads (Miltenyi Biotec, Bergisch Gladbach, Germany), and 10 6 cells/ml in RPMI-10 were pulsed with 1 mM dinitrobenzene sulfonic acidsodium salt (DNBS, MP Biomedicals, Santa Ana, CA) for 30 min at 37°C.…”