Nicotinamide Inhibits CD4+ T-Cell Activation and Function

Abstract

Chronic inflammation and autoimmune diseases are driven, in part, by the activation of (auto)reactive CD4+ T-cells, highlighting their potential as therapeutic targets for these diseases. Nicotinamide (NAM) has demonstrated anti-inflammatory properties in various disease models and has already demonstrated safety in several large clinical trials in humans. The mechanisms behind these observations, and especially their direct effects on CD4+ T-cells, remain poorly understood. Here, we address this gap by investigating how NAM influences CD4+ T-cell activation and function. We also describe that NAM treatment significantly suppresses CD4+ T-cell activation in vitro, as evidenced by impaired proliferation and reduced expression of surface activation markers. Additionally, NAM treatment resulted in reduced production of pro-inflammatory cytokines, IL-2, IFNy, and IL-17, further highlighting its anti-inflammatory potential. We found that NAM modulates key metabolic processes, including glycolysis and reactive oxygen species (ROS) production-both essential to T-cell activation. Taken together, our findings provide novel mechanistic insight into the regulation of T-cell activation by NAM, suggesting NAM as an attractive candidate for novel therapies targeting immune-related diseases.