Stress Hyperglycemia Drives CD4⁺ T Cell PANoptosis and Postoperative Organ Injury via Monocyte-Derived Succinate

Perioperative stress hyperglycemia is a transient but frequent metabolic disturbance strongly linked to postoperative organ injury and mortality; however, the immunometabolic mechanisms driving this association remain largely undefined. In a two-center cohort of patients undergoing total aortic arch replacement, we identify stress hyperglycemia as an independent determinant of poor postoperative outcomes that associates strongly with CD4⁺ T cell loss. Hyperglycemia induces inflammatory PANoptosis in CD4⁺ T cells from patients in response to surgical trauma. This results from elevated glucose driving the accumulation and release of succinate from monocytes, which subsequently acts on CD4⁺ T cells to compromise mitochondrial integrity and activate ZBP1-mediated PANoptosis. Our findings define a monocyte-T cell metabolic signaling axis that transduces hyperglycemic stress via elevated succinate to adaptive immune cell death and reveal potential therapeutic targets to prevent postoperative immune dysfunction and organ injury, especially for patients with hyperglycemic comorbidities.