Fig. 1

Metabolic reprogramming at early DC activation. Peripheral lymphoid tissue-resident DCs are ultimately of bone marrow (BM) origin via a common restricted precursor termed common dendritic monocyte precursors (CDPs), which further differentiate into DC progenitors (Pro-DCs) and pDCs. Pro-DCs become immature pre-cDC1s and pre-cDC2s with distinct metabolic programming. AMP-activated kinase (AMPK) (A) or fatty acid oxidation (FAO) (F) promote pre-cDC1 differentiation, and reactive oxygen species (ROS) (R) skew DC differentiation toward pre-cDC2. In the periphery, pre-DCs become immature DCs that produce glycogen through glycogen synthesis (Y). Here, cDC1s rely on more OXPHOS (O) and glycolysis (G) than cDC2s. Glycolysis is highly induced under DC activation and maturation, which is supported by glycogen storage and fuels fatty acid synthesis (S). During the formation of mature immunogenic DCs, the DC antigen presentation process is affected by mTOR (T), while cDC1s support their cross-presentation function through the establishment of distinct and tightly regulated metabolic processes, including glycolysis, oxidative phosphorylation (O), mitochondria (M) and fatty acid metabolism. Mo-DC, monocyte-derived DC; Mi-DC, migration DC