SUPPLEMENTATION WITH NICOTINAMIDE RIBOSIDE ATTENUATES T CELL EXHAUSTION AND IMPROVES SURVIVAL IN SEPSIS

Area of Science:

• Immunology
• Cellular Biology
• Sepsis Research

Background:

• T cell exhaustion is a primary driver of sepsis-induced immunosuppression and poor patient outcomes.
• The role of Nicotinamide adenine dinucleotide (NAD+) in sepsis-induced T cell exhaustion is not fully understood.
• Nicotinamide ribose (NR) is a precursor to NAD+.

Purpose of the Study:

• To investigate the effect of Nicotinamide ribose (NR) supplementation on T cell exhaustion in a sepsis model.
• To explore the involvement of the NAD+/Sirtuins 1 (SIRT1) pathway in sepsis-induced immunosuppression.

Main Methods:

• Utilized a classic cecal ligation and puncture (CLP) induced sepsis animal model.
• Administered NR supplementation post-CLP.
• Assessed NAD+ and SIRT1 levels in T cells, immune cell populations (mononuclear cells, T lymphocytes, CD4+, CD8+, Th1, Th2, regulatory T cells), programmed cell death 1 (PD-1) expression, bacterial load, organ damage, and mortality.

Main Results:

• NR supplementation increased NAD+ and SIRT1 levels in T cells of septic mice.
• NR treatment mitigated spleen lymphocyte depletion, enhanced CD4+ and CD8+ T cell counts, and modulated Th1/Th2 balance.
• NR inhibited regulatory T cell expansion and PD-1 expression, reduced bacterial load, organ damage, and decreased mortality.

Conclusions:

• Nicotinamide ribose (NR) demonstrates a beneficial effect in mitigating sepsis and associated T cell exhaustion.
• The protective effects of NR are linked to the restoration of the NAD+/SIRT1 pathway.
• NR holds potential as a therapeutic strategy for sepsis management.