Immune-metabolic crosstalk in type 2 diabetes and its target-organ complications: The liver, pancreatic islet, and beyond

Type 2 diabetes (T2D) is increasingly understood as a disease of disrupted immune-metabolic crosstalk rather than metabolic dysfunction alone. Chronic low-grade inflammation, altered cytokine signaling, and immune cell infiltration are now recognized as active drivers of insulin resistance, β-cell and α-cell dysfunction, and the progression of T2D-associated organ damage. Unlike the autoimmune β-cell destruction that characterizes type 1 diabetes, the immune-metabolic disturbances in T2D arise from a distinct mechanistic axis: lipotoxicity, mitochondrial stress, and innate immune activation within metabolically active tissues, including the liver, pancreatic islet, kidney, and skeletal muscle.Two organs are particularly central to this process. In metabolic dysfunction-associated steatotic liver disease (MASLD), altered hepatic lipid metabolism triggers immune cell activation (Kupffer cells, monocyte-derived macrophages) and drives progression from simple steatosis to inflammation and fibrosis. In the pancreatic islet, chronic metabolic stress disrupts not only insulin-secreting β-cells but also glucagon-secreting α-cells, with mitochondrial dysfunction and immune-metabolic signalling contributing to hyperglucagonemia and worsening glycemic control. These same immune-metabolic mechanisms extend beyond the liver and islet to drive T2D-associated complications, including diabetic kidney disease and diabetic myopathy, where innate immune pathways (such as cGAS-STING signalling) and impaired autophagy have been implicated in tissue injury.This Research Topic aims to bring together research that maps the shared and organ-specific immune-metabolic mechanisms driving T2D pathophysiology and its complications. We are particularly interested in mechanistic studies that connect local immune activation to metabolic dysfunction across these interconnected target organs, and in therapeutic strategies (including cell-based and exosome therapies) that intervene in this axis.We welcome original research articles, reviews, mini-reviews, and perspectives addressing, but not limited to, the following themes:• Mechanisms of immune cell activation and lipid-driven inflammation in hepatic steatosis and MASLD progression in the context of T2D and insulin resistance• Immune-metabolic dysregulation of pancreatic α- and β-cell function, including mitochondrial stress and its contribution to hyperglucagonemia and glycemic dysregulation• Innate immune signalling pathways (e.g., cGAS-STING, inflammasome activation) driving tissue injury in diabetic kidney disease and other T2D-associated organ complications• Autophagy and mitochondrial quality control as shared regulatory nodes linking metabolic stress to immune activation across target organs• Mesenchymal stromal cell- and exosome-based therapeutic approaches for modulating immune-metabolic dysfunction in T2D and its complications• Cross-organ signalling and systemic metabolic-immune crosstalk linking hepatic, pancreatic, renal, and muscular dysfunction in T2D• Biomarkers of immune-metabolic dysfunction with diagnostic or prognostic relevance across T2D-associated tissue complications Topic editors: Xinghong Guo, Guochang Hu, Kae Won Cho, Nan Zang Source: https://www.frontiersin.org/research-topics/85425/immune-metabolic-crosstalk-in-type-2-diabetes-and-its-target-organ-complications-the-liver-pancreatic-islet-and-beyond