GABA regulates IL-1b production in macrophages

作者：Fu, Jian; Han, Ziyi; Wu, Zebiao; Xia, Yaoyao; Yang, Guan; Yin, Yulong^*; Ren, Wenkai^*

来源：Cell Reports, 2022, 41(10): 111770.

DOI：10.1016/j.celrep.2022.111770

• LYSINE
• IMMUNOMETABOLISM
• MUTATIONS
• RESPONSES

Neurotransmitters have been well documented to determine immune cell fates; however, whether and how g-amino butyric acid (GABA) shapes the function of innate immune cells is still obscure. Here, we demon-strate that GABA orchestrates macrophage maturation and inflammation. GABA treatment during macro-phage maturation inhibits interleukin (IL)-1b production from inflammatory macrophages. Mechanistically, GABA enhances succinate-flavin adenine dinucleotide (FAD)-lysine specific demethylase1 (LSD1) signaling to regulate histone demethylation of Bcl2l11 and Dusp2, reducing formation of the NLRP3-ASC-Caspase-1 complex. The GABA-succinate axis reduces succinylation of mitochondrial proteins to promote oxidative phosphorylation (OXPHOS). We also find that GABA alleviates lipopolysaccharides (LPS)-induced sepsis as well as high-fat-diet-induced obesity in mice. Our study shows that GABA regulates pro-inflammatory macrophage responses associated with metabolic reprogramming and protein succinylation, suggesting a strategy for treating macrophage-related inflammatory diseases.

• 单位
  中国科学院; 华南农业大学