Metabolic Plasticity in Dendritic Cell Responses: Implications in Allergic Asthma

Abstract

Dendritic cells (DCs) are highly specialized in antigen presentation and play a pivotal role in the initiation, progression, and perpetuation of adaptive immune responses. Emerging immune pathways are being recognized increasingly for DCs and their subsets that differentially regulate T lymphocyte function based on the type and interactions with the antigen. However, these interactions not only alter the signaling process and DC function but also render metabolic plasticity. The current review focuses on the metabolic cues of DCs that coordinate DC activation and differentiation and discuss whether targeting these fundamental cellular processes have implications to control airway inflammation and adaptive immunity. Therefore, strategies using metabolism-based therapeutic manipulation of DC functions could be developed into novel treatments for airway inflammation and asthma.

Figure 1

Basic preferences of DC metabolism. DCs originates from the common dendritic progenitors (CDPs) in the bone marrow (BM) that use mitochondrial oxidative phosphorylation (OXPHOS) as a key metabolic energy source and have increased mitochondrial biogenesis. These DC-committed progenitors egress the BM and circulate in the bloodstream and tissues as naïve immature DCs that promoted mitochondrial OXPHOS and shifted with the metabolic preferences upon allergen uptake and toll-like receptor (TLR) activation. The early glycolytic surge in activated DCs is primarily mediated via AKT pathways that phosphorylate and activate hexokinase II (the rate-limiting enzyme of the glycolytic pathway), whereas a late-occurring event of increased glycolysis is maintained by activated mTORC-HIF1α and is NO-dependent. NO: nitric oxide; mTORC1: mammalian target of rapamycin complex 1; HIF1α: hypoxia-inducible factor 1-alpha.