Abstract
Intracellular metabolic programs tightly regulate the functions of macrophages, and previous studies have shown that serine mainly shapes the macrophage function via one-carbon metabolism. However, it is unknown whether serine modulates the macrophage function independent of one-carbon metabolism. Here, we find that serine deprivation lowers interleukin (IL)-1β production and inflammasome activation, as well as reprograms the transcriptomic and metabolic profile in M1 macrophages. Intriguingly, supplementation of formate, glycine, dNTPs, and glucose cannot rescue the production of IL-1β from serine-deprived macrophages. Mechanistically, serine deprivation inhibits macrophage IL-1β production through inhibition of mechanistic target of rapamycin (mTOR) signaling. Of note, the macrophages from mice feeding serine-free diet have lower IL-1β production, and these mice also show less inflammation after LPS challenge. Collectively, our data highlight a new regulatory mechanism for serine to modulate the macrophage function.
Highlights
Macrophages are essential components for resisting pathogen infection, repairing damaged tissue, and maintaining immune homeostasis [1, 2]
Serine deprivation lowered the mRNA expression of IL-1β and TNFα in M1 macrophages, while serine supplementation boosted the expression of these genes (Figure 1B)
Serine is a non-essential amino acid that used for the one-carbon metabolism, which supports nucleotide, SAM, NADPH, and GSH synthesis [30]
Summary
Macrophages are essential components for resisting pathogen infection, repairing damaged tissue, and maintaining immune homeostasis [1, 2]. M2 macrophages induced by IL-4 and/or IL-13 show anti-inflammatory phenotype and repair damaged tissue [4, 5]. The Serine and mTOR in IL-1β Production metabolic characteristics in M2 macrophages include mitochondrial oxidative phosphorylation (OXPHOS) and fatty acid oxidation, and an intact tricarboxylic acid (TCA) cycle [8]. In addition to these metabolic differences, M1 macrophages and M2 macrophages differ in amino acid metabolism. There is growing interest in serine metabolism in fate decision of macrophages
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