CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions.

ABSTRACT: Exposure of lipopolysaccharide triggers macrophage pro-inflammatory polarization accompanied by metabolic reprogramming, characterized by elevated aerobic glycolysis and a broken tricarboxylic acid cycle. However, in contrast to lipopolysaccharide, CD40 signal is able to drive pro-inflammatory and anti-tumorigenic polarization by some yet undefined metabolic programming. Here we show that CD40 activation triggers fatty acid oxidation (FAO) and glutamine metabolism to promote ATP citrate lyase-dependent epigenetic reprogramming of pro-inflammatory genes and anti-tumorigenic phenotypes in macrophages. Mechanistically, glutamine usage reinforces FAO-induced pro-inflammatory and anti-tumorigenic activation by fine-tuning the NAD⁺/NADH ratio via glutamine-to-lactate conversion. Genet

SUBMITTER: Liu PS 

PROVIDER: S-EPMC9977680 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature