炎症
先天免疫系统
细胞生物学
巨噬细胞
化学
琥珀酰化
免疫系统
生物化学
生物
赖氨酸
免疫学
氨基酸
体外
作者
Jian Fu,Zi‐Yi Han,Zebiao Wu,Yaoyao Xia,Guan Yang,Yulong Yin,Wenkai Ren
出处
期刊:Cell Reports
[Elsevier]
日期:2022-12-01
卷期号:41 (10): 111770-111770
被引量:22
标识
DOI:10.1016/j.celrep.2022.111770
摘要
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.
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