The article "Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases" by Carolina Ferreira et al. explores the role of polyphenols in modulating immune responses and their potential to alleviate chronic low-grade inflammation. Polyphenols, a class of secondary metabolites abundant in Mediterranean foods, exhibit immunomodulatory actions through a mitochondria-centered multi-modal approach. They activate nutrient sensing pathways, regulate the mTOR/AMPK balance, interfere with NLRP3 assembly, and impact chromatin remodeling. These effects contribute to the reprogramming of immune cells towards a less inflamed, tolerogenic phenotype. The article highlights the importance of polyphenols in both innate and adaptive immunity, including their effects on dendritic cells, monocytes, macrophages, neutrophils, and natural killer (NK) cells. Additionally, it discusses the potential of polyphenols in treating autoimmune and non-autoimmune metabolic disorders, such as type 1 diabetes mellitus (T1DM), by improving mitochondrial function and modulating immune cell polarization. The authors propose that polyphenols could serve as precise immunonutritional interventions to address the increasing prevalence of chronic diseases with immunometabolic impairments.The article "Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases" by Carolina Ferreira et al. explores the role of polyphenols in modulating immune responses and their potential to alleviate chronic low-grade inflammation. Polyphenols, a class of secondary metabolites abundant in Mediterranean foods, exhibit immunomodulatory actions through a mitochondria-centered multi-modal approach. They activate nutrient sensing pathways, regulate the mTOR/AMPK balance, interfere with NLRP3 assembly, and impact chromatin remodeling. These effects contribute to the reprogramming of immune cells towards a less inflamed, tolerogenic phenotype. The article highlights the importance of polyphenols in both innate and adaptive immunity, including their effects on dendritic cells, monocytes, macrophages, neutrophils, and natural killer (NK) cells. Additionally, it discusses the potential of polyphenols in treating autoimmune and non-autoimmune metabolic disorders, such as type 1 diabetes mellitus (T1DM), by improving mitochondrial function and modulating immune cell polarization. The authors propose that polyphenols could serve as precise immunonutritional interventions to address the increasing prevalence of chronic diseases with immunometabolic impairments.