UV Irradiation of Skin Enhances Glycolytic Flux and Reduces Migration Capabilities in Bone Marrow-Differentiated Dendritic Cells.

In this study, dendritic cells (DCs) differentiating from the bone marrow 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 bone marrow 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 bone marrow of nonirradiated mice, those from UV-irradiated mice produced more lactate, used greater amounts of 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 bone marrow of UV-irradiated mice. UV-induced prostaglandin E2 has been implicated as an intermediary in the effects of UV radiation on bone marrow cells. DCs differentiating from bone marrow cells pulsed in vitro for 2 hours with dimethyl prostaglandin E2 were functionally similar to those from the bone marrow 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-irrad...

Source: The American Journal of Pathology - July 11, 2017 Category: Pathology Authors: McGonigle TA, Keane KN, Ghaly S, Carter KW, Anderson D, Scott NM, Goodridge HS, Dwyer A, Greenland E, Pixley FJ, Newsholme P, Hart PH Tags: Am J Pathol Source Type: research