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

Abstract

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 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 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.

The Ontogeny of Monocyte Subsets

“…Beyond microbial infection, it is likely that other stimuli also impact the functional programming of monocytes during differentiation, whether or not they concomitantly boost monocyte numbers. For instance, PGE2 induced by UV skin irradiation causes epigenetic and metabolic changes in bone marrow progenitors, and the monocytes, macrophages and DCs they produce have a restricted capacity to migrate in response to chemoattractants and inflammatory mediators (52–55). Immunosuppressive monocytes produced in the context of tumors may also acquire their suppressive properties during differentiation, because monocytic cells isolated from the circulation, spleen and bone marrow of cancer patients and tumor-bearing mice have been reported to inhibit T cell activation and promote tumor growth (4, 5, 56).…”

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood

“…Thus, despite the sparse evidence, it seems unlikely that exposure to UVR affects the number of circulating DCs or subsets significantly. Functional and migratory tests on blood DCs have not been carried out thus far although murine tests suggest their function may be reduced (40)(41)(42).…”

Metabolic dysfunction induced by high-fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice

“…Further experiments are needed to demonstrate if there are functional links between reductions in TNF levels and cDC in iBAT of mice exposed to UVR. Other studies indicate that UVR exposure can mediate functional changes in DCs derived from myeloid progenitors in bone marrow, including enhanced glycolytic flux, reduced migration and impaired capacity to prime immune responses [27][28][29][30] .…”