SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing

干扰素基因刺激剂 生物 肝X受体 信号转导 细胞生物学 磷酸二酯酶 生物化学 先天免疫系统 受体 基因 核受体 转录因子 航空航天工程 工程类
作者
Yanfei Hou,Zhimeng Wang,Peiyuan Liu,Xubiao Wei,Zhengyin Zhang,Shilong Fan,Lulu Zhang,Fangping Han,Yin Song,Ling Chu,Conggang Zhang
出处
期刊:Immunity [Elsevier]
卷期号:56 (11): 2492-2507.e10 被引量:3
标识
DOI:10.1016/j.immuni.2023.10.001
摘要

Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified liver X receptor (LXR) agonists as potent inhibitors of STING signaling. We show that stimulation of lipid metabolism by LXR agonists specifically suppressed cyclic GMP-AMP (cGAMP)-STING signaling. Moreover, we developed cyclic dinucleotide-conjugated beads to biochemically isolate host effectors for cGAMP inhibition, and we found that LXR ligands stimulated the expression of sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), which is a 2'3'-cGAMP-degrading enzyme. Results of crystal structures suggest that cGAMP analog induces dimerization of SMPDL3A, and the dimerization is critical for cGAMP degradation. Additionally, we have provided evidence that SMPDL3A cleaves cGAMP to restrict STING signaling in cell culture and mouse models. Our results reveal SMPDL3A as a cGAMP-specific nuclease and demonstrate a mechanism for how LXR-associated lipid metabolism modulates STING-mediated innate immunity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
年轻白昼发布了新的文献求助10
1秒前
bkagyin应助joye采纳,获得10
1秒前
zzz发布了新的文献求助10
2秒前
傅宛白发布了新的文献求助10
4秒前
4秒前
4秒前
5秒前
十三完成签到,获得积分10
6秒前
7秒前
Levelsinc完成签到,获得积分10
7秒前
深情安青应助幸福的冰珍采纳,获得10
7秒前
7秒前
8秒前
8秒前
8秒前
明月发布了新的文献求助10
9秒前
上官若男应助俊逸的雁凡采纳,获得10
9秒前
9秒前
不安青牛应助aldwd采纳,获得10
10秒前
SOLOMON应助互助遵法尚德采纳,获得10
10秒前
soar发布了新的文献求助10
10秒前
土豆发布了新的文献求助10
11秒前
小李发布了新的文献求助10
12秒前
12秒前
13秒前
13秒前
852应助傅宛白采纳,获得10
14秒前
张泽崇应助ads采纳,获得10
14秒前
阿巴阿巴完成签到,获得积分10
15秒前
香蕉觅云应助lsssszb采纳,获得10
15秒前
wzz完成签到,获得积分10
15秒前
bk一201一完成签到 ,获得积分10
15秒前
SJD完成签到,获得积分0
15秒前
hfgeyt发布了新的文献求助10
16秒前
16秒前
17秒前
19秒前
晨曦发布了新的文献求助10
19秒前
22秒前
卡萨卡萨完成签到,获得积分10
23秒前
高分求助中
Manual of Clinical Microbiology, 4 Volume Set (ASM Books) 13th Edition 1000
Teaching Social and Emotional Learning in Physical Education 900
Chinese-English Translation Lexicon Version 3.0 500
Electronic Structure Calculations and Structure-Property Relationships on Aromatic Nitro Compounds 500
マンネンタケ科植物由来メロテルペノイド類の網羅的全合成/Collective Synthesis of Meroterpenoids Derived from Ganoderma Family 500
[Lambert-Eaton syndrome without calcium channel autoantibodies] 440
Plesiosaur extinction cycles; events that mark the beginning, middle and end of the Cretaceous 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2383063
求助须知:如何正确求助?哪些是违规求助? 2090168
关于积分的说明 5253417
捐赠科研通 1817095
什么是DOI,文献DOI怎么找? 906505
版权声明 558965
科研通“疑难数据库(出版商)”最低求助积分说明 484013