Hyperglycemic Memory of Innate Immune Cells Promotes In Vitro Proinflammatory Responses of Human Monocytes and Murine Macrophages

Abstract It has been well established that the presence of diabetes is accompanied by a chronic inflammatory state promoting various diabetes-associated complications. One potential driver this enhanced in patients with hyperglycemia. Even after blood glucose control achieved, complications persist, suggesting “hyperglycemic memory.” Innate immune cells, critically involved associated diabetes, can build nonspecific, immunological memory (trained immunity) via epigenetic regulation. We examine involvement hyperglycemia-induced trained immunity inflammation. Our results show hyperglycemia induces phenotype vivo mice and vitro human monocytes, representative an increased TNF-? secretion ex stimulation LPS. These effects were largely mediated changes controlled mixed lineage leukemia (MLL) family because treatment MLL inhibitor menin-MLL during process acquisition repressed proinflammatory phenotype. Collectively, our identify novel link between inflammation innate cells might explain potentially contributing to development