UV Irradiation of Skin Enhances Glycolytic Flux and Reduces Migration Capabilities in Bone Marrow–Differentiated Dendritic Cells
MetadataShow full item record
A systemic immunosuppression follows UV irradiation of the skin of humans and mice. In this study, dendritic cells (DCs) differentiating from the bone marrow (BM) of UV-irradiated mice had a reduced ability to migrate toward the chemokine (C-C motif) ligand 21. Fewer DCs also accumulated in the peritoneal cavity of UV-chimeric mice (ie, mice transplanted with BM from UV-irradiated mice) after injection of an inflammatory stimulus into that site. We hypothesized that different metabolic states underpin altered DC motility. Compared with DCs from the BM of nonirradiated mice, those from UV-irradiated mice produced more lactate, consumed more glucose, and had greater glycolytic flux in a bioenergetics stress test. Greater expression of 3-hydroxyanthranilate 3,4-dioxygenase was identified as a potential contributor to increased glycolysis. Inhibition of 3-hydroxyanthranilate 3,4-dioxygenase by 6-chloro-DL-tryptophan prevented both increased lactate production and reduced migration toward chemokine (C-C motif) ligand 21 by DCs differentiated from BM of UV-irradiated mice. UV-induced prostaglandin E 2 has been implicated as an intermediary in the effects of UV radiation on BM cells. DCs differentiating from BM cells pulsed in vitro for 2 hours with dimethyl prostaglandin E 2 were functionally similar to those from the BM of UV-irradiated mice. Reduced migration of DCs to lymph nodes associated with increased glycolytic flux may contribute to their reduced ability to initiate new immune responses in UV-irradiated mice.
Showing items related by title, author, creator and subject.
Reticulon-1 and reduced migration toward chemoattractants by macrophages differentiated from the bone marrow of ultraviolet-irradiated and ultraviolet-chimeric miceMcGonigle, T.; Dwyer, A.; Greenland, E.; Scott, N.; Carter, K.; Keane, Kevin; Newsholme, P.; Goodridge, H.; Pixley, F.; Hart, P. (2018)The ability of macrophages to respond to chemoattractants and inflammatory signals is important for their migration to sites of inflammation and immune activity and for host responses to infection. Macrophages differentiated ...
Hart, P.; McGonigle, T.; Keane, K.; Newsholme, Philip; Ghaly, S.; Carter, K.; Anderson, D.; Scott, N.; Goodridge, H. (2016)Following UV irradiation of skin, dendritic cells (DCs) differentiating from the bone marrow (BM) of mice have a reduced ability to prime new immune responses; their reduced immunogenicity is maintained for at least 16 ...
Disruption of blood-brain barrier function by chronic intake of saturated fat and cholesterol : implications for Alzheimer’s disease riskTakechi, Ryusuke (2010)It has been reported that lifestyle including diet is associated with Alzheimer’s disease (AD) risk and progression. Population studies indicate that the chronic consumption of diets enriched in saturated fats (SFA) and ...