Immune dysregulation and immunoengineering strategies for type 2 diabetes

Type 2 diabetes (T2D) is increasingly recognized as an immunometabolic disease, in which chronic inflammation and immune dysregulation contribute to insulin resistance, β-cell dysfunction, and systemic metabolic impairment. Immune alterations occur across multiple metabolic organs and are coordinated through complex inter-organ communication networks involving cytokines, metabolites, extracellular vesicles, and microbial signals. These findings have identified immune homeostasis as a promising therapeutic target for T2D and have gained increasing support with advances in immunoengineering strategies. In this review, we first summarize the mechanisms of immune dysregulation in the pathogenesis of T2D, and then discuss emerging immunoengineering approaches designed to restore metabolic and immune homeostasis, including nanomaterial-based drug delivery systems, immune cell engineering, cell-derived vesicles, and microbiota-based therapeutics. Finally, we outline key challenges related to immunological heterogeneity, safety, and clinical translation, and highlight future directions toward personalized and precise immunometabolic therapies for T2D.