GABA regulates IL-1β production in macrophages

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

23 Scopus Citations
View graph of relations

Author(s)

  • Jian Fu
  • Ziyi Han
  • Zebiao Wu
  • Yaoyao Xia
  • Yulong Yin
  • Wenkai Ren

Detail(s)

Original languageEnglish
Article number111770
Journal / PublicationCell Reports
Volume41
Issue number10
Online published6 Dec 2022
Publication statusPublished - 6 Dec 2022

Link(s)

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.

Research Area(s)

  • CP: Immunology, FAD, GABA, macrophage, succinate, succinylation

Citation Format(s)

GABA regulates IL-1β production in macrophages. / Fu, Jian; Han, Ziyi; Wu, Zebiao et al.
In: Cell Reports, Vol. 41, No. 10, 111770, 06.12.2022.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

Download Statistics

No data available