한김계영 (NHLBI-NIH) | 한빛사논문 > 한빛사

한빛사논문

조회563

NHLBI-NIH

CV File 332 kb

Cell Rep. Med., 2023 Aug 9;101157 | https://doi.org/10.1016/j.xcrm.2023.101157 Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects

Kim Han ¹, Komudi Singh ¹, Allison M. Meadows ^{1 2}, Rahul Sharma ¹, Shahin Hassanzadeh ¹, Jing Wu ¹, Haley Goss-Holmes ¹, Rebecca D. Huffstutler ³, Heather L. Teague ⁴, Nehal N. Mehta ⁴, Julian L. Griffin ^{2 5}, Rong Tian ⁶, Javier Traba ^{1 7 8}, Michael N. Sack ^{1 2 9 *}

¹Laboratory of Mitochondrial Biology and Metabolism, NHLBI, NIH, Bethesda, MD, USA
²Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK
³Cardiovascular Branch, NHLBI, NIH, Bethesda, MD, USA
⁴Laboratory of Cardiometabolic Disease and Inflammation, NHLBI, NIH, Bethesda, MD, USA
⁵The Rowett Institute, School of Medicine, Medical Sciences and Nutrition, Foresterhill Campus, Aberdeen, UK
⁶Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA, USA
⁷Instituto Universitario de Biología Molecular-UAM (IUBM-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain
⁸Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas—Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain
⁹Lead contact

^*Corresponding author: correspondence to Michael N. Sack

Abstract

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.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-08-22)
연구진국외 연구진
분야 의약학 > 면역의학

댓글 작성 로그인

CV 열람하기

연락처 보기