2. Academic Validation
  3. GABA regulates IL-1β production in macrophages

GABA regulates IL-1β production in macrophages

  • Cell Rep. 2022 Dec 6;41(10):111770. doi: 10.1016/j.celrep.2022.111770.
Jian Fu 1,  Ziyi Han 1,  Zebiao Wu 1,  Yaoyao Xia 1,  Guan Yang 2,  Yulong Yin 3,  Wenkai Ren 4
Affiliations

Affiliations

  • 1 Guangdong Laboratory of Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
  • 2 Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong SAR 999077, China.
  • 3 Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China. Electronic address: [email protected].
  • 4 Guangdong Laboratory of Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China. Electronic address: [email protected].
PMID: 36476877 DOI: 10.1016/j.celrep.2022.111770
Abstract

Neurotransmitters have been well documented to determine immune cell fates; however, whether and how γ-amino butyric acid (GABA) shapes the function of innate immune cells is still obscure. Here, we demonstrate that GABA orchestrates macrophage maturation and inflammation. GABA treatment during macrophage maturation inhibits interleukin (IL)-1β 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.

Keywords

CP: Immunology; FAD; GABA; macrophage; succinate; succinylation.

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