Sirtuins in inflammation and autoimmunity

Abstract

Sirtuins, a conserved family of nicotinamide adenine dinucleotide-dependent deacetylases, are key regulators of immune balance, inflammation, and autoimmunity. This chapter examines the dual functions of sirtuin isoforms (SIRT1–SIRT7) in controlling innate and adaptive immunity via transcriptional and posttranslational mechanisms. They affect critical inflammatory pathways, such as NF-κB, STAT3, and NLRP3 inflammasome activation, influencing cytokine, chemokine, and adhesion molecule expression. SIRT1 suppresses proinflammatory genes by deacetylating NF-κB p65, while SIRT6 impacts TNF-α secretion and macrophage polarization. The chapter discusses the variation in sirtuin expression and function in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Animal models lacking sirtuins offer insights into autoimmune development and inflammation resolution. The potential of sirtuin modulators such as resveratrol, SRT2104, and other compounds is evaluated using preclinical and clinical data. The chapter also addresses challenges such as tissue specificity, isoform selectivity, and context-dependent effects that hinder clinical translation. Overall, it emphasizes the promising yet complex role of sirtuins as therapeutic targets for inflammation and autoimmunity, emphasizing the need for further research.