Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects.
Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects.
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DOI：
10.1016/j.xcrm.2023.101157
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发表时间：
2023-09-19
影响因子：
14.3
通讯作者：
Sack, Michael N.
中科院分区：
文献类型：
--
作者：
Han, Kim;Singh, Komudi;Meadows, Allison M.;Sharma, Rahul;Hassanzadeh, Shahin;Wu, Jing;Goss-Holmes, Haley;Huffstutler, Rebecca D.;Teague, Heather L.;Mehta, Nehal N.;Griffin, Julian L.;Tian, Rong;Traba, Javier;Sack, Michael N.
为了评估烟酰胺腺嘌呤二核苷酸阳性（NAD+）加强是否调节适应性免疫，将来自健康对照和银屑病受试者的原代CD 4 + T细胞暴露于媒介物或烟酰胺核苷（NR）补充。NR使干扰素γ（IFNγ）和白细胞介素（IL）-17分泌减弱，对辅助性T细胞（Th）17极化的影响更大。RNA测序（RNA-seq）分析表明，NR钝化螯合体1（sqstm 1/p62）耦合的氧化应激。NR给药增加sqstm 1并降低活性氧（ROS）水平。此外，NR激活核因子红细胞2相关因子2（Nrf 2），nrf 2和Nrf 2依赖性基因sqstm 1的遗传敲低，减少NR改善效果。代谢组学分析鉴定，NAD+加强增加精氨酸和富马酸的生物合成，并且对氨基琥珀酸裂解酶的遗传敲低改善NR对IL-17产生的影响。因此，NR通过氨基酸代谢物协调Nrf 2活化，增强CD 4 + T细胞抗氧化防御，并减弱Th 17反应性。在健康志愿者中口服NR补充剂类似地增加血清精氨酸、sqstm 1和抗氧化酶基因表达，并减弱Th 17免疫应答，支持在CD 4 + T细胞相关炎症中评估NAD+增强。NAD+如何增强炎症是知之甚少的综合转录组学和代谢组学鉴定T细胞调节途径NAD+增加精氨酸和富马酸盐的生物合成这些代谢产物，通过NRF 2信号传导，减弱Th 1和Th 17免疫反应性Han et al.研究了NAD+对炎症的促进作用，发现烟酰胺核苷补充剂减弱了健康志愿者和银屑病患者的Th 1和Th 17免疫反应。生物信息学分析揭示，NAD+通过精氨酸和富马酸盐生物合成，激活NRF 2。这反式激活抗氧化剂调节程序，钝化适应性免疫细胞炎症信号传导。
To evaluate whether nicotinamide adenine dinucleotide-positive (NAD+) boosting modulates adaptive immunity, primary CD4+ T cells from healthy control and psoriasis subjects were exposed to vehicle or nicotinamide riboside (NR) supplementation. NR blunts interferon γ (IFNγ) and interleukin (IL)-17 secretion with greater effects on T helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates NR blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. NR administration increases sqstm1 and reduces reactive oxygen species (ROS) levels. Furthermore, NR activates nuclear factor erythroid 2-related factor 2 (Nrf2), and genetic knockdown of nrf2 and the Nrf2-dependent gene, sqstm1, diminishes NR amelioratory effects. Metabolomics analysis identifies that NAD+ boosting increases arginine and fumarate biosynthesis, and genetic knockdown of argininosuccinate lyase ameliorates NR effects on IL-17 production. Hence NR via amino acid metabolites orchestrates Nrf2 activation, augments CD4+ T cell antioxidant defenses, and attenuates Th17 responsiveness. Oral NR supplementation in healthy volunteers similarly increases serum arginine, sqstm1, and antioxidant enzyme gene expression and blunts Th17 immune responsiveness, supporting evaluation of NAD+ boosting in CD4+ T cell-linked inflammation. How NAD+ boosting blunts inflammation is poorly understood Integrated transcriptomics and metabolomics identify T cell regulatory pathways NAD+ increases arginine and fumarate biosynthesis These metabolites, via NRF2 signaling, blunt Th1 and Th17 immune responsiveness Han et al. investigated NAD+-boosting effects on inflammation and found that nicotinamide riboside supplementation blunts Th1 and Th17 immune responsiveness in healthy volunteers and in psoriasis. Bioinformatics analysis uncovers that NAD+ boosting, via arginine and fumarate biosynthesis, activates NRF2. This transactivates antioxidant regulatory programs that blunt adaptive immune cell inflammatory signaling.
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影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
通讯作者：
von Mering C
DOI：
10.1073/pnas.1718819115
发表时间：
2018-02-20
影响因子：
11.1
作者：
Hou, Yujun;Lautrup, Sofie;Bohr, Vilhelm A.
通讯作者：
Bohr, Vilhelm A.
影响因子：
158.5
作者：
Chen, Andrew C.;Martin, Andrew J.;Damian, Diona L.
通讯作者：
Damian, Diona L.
影响因子：
4.8
作者：
Jain, Ashish;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
7.3
作者：
Brembilla NC;Senra L;Boehncke WH
通讯作者：
Boehncke WH