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          NIAMS Scientific Advances
          Boosting NAD Metabolism Is Involved in Monocytes IFN Type I Proinflammatory Responses








NIAMS Advances


Boosting NAD Metabolism Is Involved in Monocytes IFN Type I Proinflammatory Responses March 1, 2022
                                TRANSLATIONAL
        Mariana J. Kaplan, M.D.
                                          |
              Systemic Autoimmunity Branch
                                          |
              NIAMS IRP
        Description

An anti-inflammatory environment can be induced in humans after fasting and by increasing cellular nicotinamide adenine dinucleotide (NAD+) levels. Nicotinamide riboside (NR), an NAD+ precursor, mimics fasting effects in healthy volunteers and attenuates proinflammatory pathways. This study explored the anti-inflammatory effect of NR in healthy volunteers receiving placebo or NR treatment by analyzing their monocytes, a type of white blood cell that finds and destroys pathogens entering the body. This study used RNA-sequencing technology to analyze monocytes from both healthy people and patients with lupus to show that NR treatment suppressed inflammatory responses in patients with lupus in part through inosine signaling. The findings suggest that NR is a potential adjunct to lupus treatment.

What is exciting about this article?

A key part of SLE clinical management is decreasing proinflammatory and type I interferon (IFN) responses to prevent further tissue damage and critical cardiovascular events. This study described a mechanism by which monocytes contribute to the proinflammatory environment and suggested a potential therapeutic strategy for SLE and other diseases where proinflammation via type I IFN pathways is a key contributor.

How does this fit into the larger NIAMS portfolio?

This work leads to a greater understanding of various mechanisms that can aid in treatment design for SLE. A clinical trial to test NR efficacy in SLE treatment is under preparation.

Grant support

AR041199
        Research Areas:
            Autoimmunity
      Cell Biology
      Immunology
                                        Reference:
            Boosting NAD+ blunts TLR4-induced type I IFN in control and systemic lupus erythematosus monocytes.

    Wu J, Singh K, Lin A, Meadows AM, Wu K, Shing V, Bley M, Hassanzadeh S, Huffstutler RD, Schmidt MS, Blanco LP, Tian R, Brenner C, Pirooznia M, Kaplan MJ, Sack MN
        

                    J Clin Invest.
        
                    2022 Mar 1;
        
                    132(5).
        
                    doi: 10.1172/JCI139828
                            PMID: 35025762
        Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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