Hyperglycemic Memory of Innate Immune Cells Promotes In Vitro Proinflammatory Responses of Human Monocytes and Murine Macrophages
- 15 February 2021
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 206 (4), 807-813
- https://doi.org/10.4049/jimmunol.1901348
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 of this enhanced inflammatory state in patients with diabetes is hyperglycemia. Even after blood glucose control is achieved, diabetes-associated complications persist, suggesting the presence of a “hyperglycemic memory.” Innate immune cells, critically involved in various complications associated with diabetes, can build nonspecific, immunological memory (trained immunity) via epigenetic regulation. We examine the potential involvement of hyperglycemia-induced trained immunity in promoting inflammation. Our results show that hyperglycemia induces a trained phenotype in vivo in mice and in vitro in human monocytes, representative by an increased TNF-α secretion after ex vivo stimulation with LPS. These effects were largely mediated by epigenetic changes controlled by the mixed lineage leukemia (MLL) family because treatment with the MLL inhibitor menin-MLL during the process of trained immunity acquisition repressed the proinflammatory phenotype. Collectively, our results identify a novel link between hyperglycemia and inflammation in innate immune cells that might explain the increased proinflammatory state during diabetes potentially contributing to the development of various diabetes-associated complications.Keywords
Funding Information
- Netherlands Organization for Scientific Research (Spinoza Grant, 91616083)
- Dutch Diabetes Research Foundation (2015.82.1824)
- Dutch Heart Foundation (IN-CONTROL)
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