Cellular respiration in dendritic cells: Exploring oxygen-dependent pathways for potential therapeutic interventions

Dendritic cells (DCs) are specialized antigen-presenting cells crucial for initiating and regulating adaptive immune responses, making them promising candidates for therapeutic interventions in various immune-mediated diseases. Increasing evidence suggests that the microenvironment in which cells are cultured, as well as the milieu in which they perform their functions, significantly impact their immunomodulatory properties. Among these environmental factors, the role of oxygen in DC biology and its significance for both their in vitro generation and in vivo therapeutic application require investigation. Unlike the atmospheric oxygen level of 21 % commonly used in in vitro assays, physiological oxygen levels are much lower (3-9 %), and hypoxia (<1.3 %) is a prevalent condition of both healthy tissues and disease states. This mismatch between laboratory and physiological conditions underscores the critical need to culture and evaluate therapeutic cells under physiologically relevant oxygen levels to improve their translational relevance and clinical outcomes. This review explores the characteristic hallmarks of human DCs that are influenced by oxygen-dependent pathways, including metabolism, phenotype, cytokine secretion, and migration. Furthermore, we discuss the potential of manipulating oxygen levels to refine the generation and functionality of DCs for therapeutic purposes.