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Clinical Research and Public HealthIn-Press PreviewDermatologyImmunology Open Access | 10.1172/jci.insight.203826

NAD+ augmentation by nicotinamide riboside engages SLIT2/ROBO1 signaling to attenuate Th17 inflammation in psoriasis

Kim Han,1 Rachael J. Klein,1 Thomas C. Recupero,1 Anna Chiara Russo,1 Rahul Sharma,1 Anand K. Gupta,1 Shahin Hassanzadeh,1 Rebecca D. Huffstutler,2 Pradeep K. Dagur,3 Bryan Fisk,4 Neelam R. Redekar,4 and Michael N. Sack1

1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

Find articles by Redekar, N. in: PubMed | Google Scholar

1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

2Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

3Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, United States of America

4Integrated Data Science Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

Find articles by Sack, M. in: PubMed | Google Scholar |

Published April 28, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.203826.
Copyright © 2026, Han et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 28, 2026 - Version history
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Abstract

Enhancing NAD+ levels with nicotinamide riboside (NR) confers anti-inflammatory effects in human disease, although immunoregulatory mechanisms remain poorly characterized. We previously showed that ex vivo NR supplementation of primary CD4+ T cells from psoriatic individuals dampened immune responsiveness. To validate this in vivo, we performed a randomized, placebo-controlled NR supplementation study in individuals with mild-to-moderate psoriasis. Participants received oral NR (500 mg twice daily) or matching placebo for 4 weeks, with blood samples collected at baseline and after supplementation. NR reduced Th17 immune responsiveness. Bulk CD4+ T cell RNA-seq identified induction of the SLIT-ROBO signaling pathway. NR supplementation increased circulating SLIT2 levels and enhanced SLIT2 production in dermal fibroblasts. Pharmacologic and genetic interrogation in CD4+ T cells and fibroblasts demonstrated that SLIT2, acting through the ROBO1 receptor, inhibited Rho GTPase signaling, thereby attenuating canonical Th17 polarization and fibroblast inflammatory activation. These findings indicate that NAD+ augmentation exerts anti-inflammatory effects in psoriasis through SLIT2-ROBO1-mediated crosstalk between dermal fibroblasts and circulating CD4+ T cells, leading to suppression of Th17-driven inflammation.

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