Metabolic control of dendritic cell activation and function: recent advances and clinical implications

Abstract

Dendritic cells (DCs) are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

The NF-κB Regulator Bcl-3 Governs Dendritic Cell Antigen Presentation Functions in Adaptive Immunity

“…The ability of DCs to prime T cells has also recently been linked to a major shift in metabolic programming from oxidative phosphorylation to aerobic glycolysis (40). A similar switch occurs in highly proliferative and stressed tumor cells and activated lymphocytes.…”

Metabolomics in rheumatic diseases: desperately seeking biomarkers

“…Metabolic changes occurring in T cells 106–110 , macrophages 111 and dendritic cells 112,113 have been extensively reviewed, but less information is available with regard to stromal cells, including fibroblasts, and endothelial cells 105 . Emerging evidence also indicates that metabolism is not only involved in the determination of cell differentiation and function, but also that metabolic changes contribute to the pathogenesis of cancer, diabetes and inflammatory diseases 105 .…”

Metabolic Factors that Contribute to Lupus Pathogenesis

“…Glycolysis is therefore a prime requisite for activation of DCs. 36, 188 DC differentiation from monocytes in the presence of GM-CSF and IL-4 turns on mitochondrial biogenesis by up-regulating peroxisome proliferator-activated receptor γ coactivator-1α expression. Blocking the ETC abolished DC differentiation, showing the complete dependence on mitochondria for initiating DC differentiation.…”

“…Citrate accrual during this process serves as an intermediate for FA synthesis, thus showing parallels for the requirement of FA synthesis in both differentiated and activated DCs. 36, 188 …”