UV irradiation of skin enhances glycolytic flux and reduces migration capabilities in bone marrow-differentiated dendritic cells

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 peri...

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Bibliographic Details
Published in:The American Journal of Pathology
Main Authors: McGonigle, T.A., Keane, K.N., Ghaly, S., Carter, K.W., Anderson, D., Scott, N.M., Goodridge, H.S., Dwyer, A., Greenland, E., Pixley, F.J., Newsholme, P., Hart, P.H.
Format: Article in Journal/Newspaper
Language:English
Published: Elsevier 2017
Subjects:
Dendritic Cells
Greenland
Denise
Dwyer
Online Access:http://hdl.handle.net/2440/123258
https://doi.org/10.1016/j.ajpath.2017.06.003
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Summary: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 E2 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 E2 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. Terence A. McGonigle, Kevin N. Keane, y Simon Ghaly, Kim W. Carter, Denise Anderson, Naomi M. Scott, Helen S. Goodridge, Amy Dwyer, Eloise Greenland, Fiona J. Pixley, Philip Newsholme, and Prue H. Hart

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