Rejuvenating immune cells targeting hepatitis B involves using nicotinamide mononucleotide (NMN) to reinstate their DNA repair processes and antiviral capabilities.Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), enhances the antiviral activation of immune cells (CD8 T cells) specific to the hepatitis B virus.Immune cells CD8 T cells dedicated to combatting hepatitis B, which have become exhausted and less functional, exhibit elevated DNA damage and malfunctioning DNA repair mechanisms.During their state of exhaustion, CD8 T immune cells show increased activity of the NAD+-consuming enzyme CD38 and reduced production of antiviral proteins. Hepatitis B usually gets better in almost six months in most instances. However, chronic cases arising from CD8 T cell exhaustion remain present for much longer. CD8 T cell exhaustion occurs due to extensive exposure to pathogens such as the virus of hepatitis B, causing damage to T cell DNA and an impaired antiviral response. Figuring out the cellular mechanisms resulting in this exhaustion holds potential for developing therapies against the chronic form of hepatitis B. Recent propositions suggest that NAD+ depletion might underlie T cell exhaustion. A study published by Fisicaro and his team in the Journal of Hepatology, revealed that treating hepatitis B virus-specific CD8 T cells with NMN enhances the production of cytokines, antiviral proteins. Worn-out CD8 T cells displayed heightened DNA damage levels and malfunctioning DNA repair mechanisms. The study’s findings imply that nicotinamide mononucleotide supplement or CD38 inhibitors may rejuvenate exhausted T cells, potentially combating chronic hepatitis B and other viral infections. NMN Supplement And Immune Cell Antiviral Activation To test how NMN could restore NAD+ levels and rejuvenate exhausted CD8 T cells, Fisicaro and the team extracted these immune cells from individuals with chronic type of hepatitis B. Following NMN supplement treatment, the cells displayed elevated antiviral cytokines levels, particularly a 2.7-times increase in interferon gamma (IFN-𝛾) cytokine. This indicates NMN’s ability to reinstate the antiviral properties of CD8 T cells. In assessing cellular damage linked to T cell exhaustion during hepatitis B chronic infection, the researchers compared DNA damage found in hepatitis B-specific T cells with those specific to influenza (FLU). Remarkably higher levels of DNA damage were observed in the hepatitis B-specific T cells. Treating these cells with DNA-damaging etoposide led to diminished DNA damage response in comparison with FLU-specific T cells. As DNA damage responses, such as the one moderated by PARPs, necessitate NAD+, this study offers a connection between NAD+ deficiency and increased DNA damage levels in exhausted hepatitis B-specific CD8 T cells. Delving deeper into the relationship between NAD+ repletion through NMN and enhanced antiviral cytokine production in exhausted CD8 T cells, Fisicaro and colleagues scrutinised the interplay between the NAD+-consuming enzyme CD38 and cytokine levels. The researchers assessed IFN-𝛾, one of the key cytokines, and discovered that elevated CD38 enzyme levels corresponded to lower IFN-𝛾 levels. This correlation supports the idea that increased levels of CD38 enzyme hinder antiviral cytokine generation and reinforces the notion that decreased NAD+ levels significantly contribute to the progression of chronic hepatitis B, as heightened CD38 levels would deplete cellular NAD+. Fisicaro and colleagues imply that NAD+-devouring enzymes, especially overexpressed CD38, potentially play a huge part in NAD+ depletion. The restoration of numerous interconnected functions within cells through NMN supplementation suggests that the decline of NAD+ is probably a key factor in driving T cell exhaustion. The Role of NMN Supplement in Restoring Immune Cells This study suggests that heightened activation of the CD38 enzyme is due to stimulation by the hepatitis B virus, resulting in reduced NAD+ levels. Given that DNA repair mechanisms, such as PARPs, rely on NAD+ supplement, this could explain the enhanced DNA damage observed in exhausted hepatitis B-specific T cells. This might also explain the reduced effectiveness of DNA repair processes in CD8 T cells, specifically exhausted hepatitis B virus-specific T cells. The treatment of CD8 T immune cells with NMN effectively reinstates the generation of antiviral cytokines, showing that NAD+ replenishment reinstates their function. The ability of NMN to enhance immune cell performance strengthens the notion of NAD+ depletion contributing to CD8 T cell exhaustion and malfunction. The prospect of NMN’s positive impact on depleted CD8 T cells in different infections warrants investigation. If NMN succeeds in revitalising depleted T cells across various infections, it will suggest NAD+ might enhance immune cells’ ability to combat diverse infections as well.