New CELL METABOLISM paper by the groups of Radboud University Nijmegen
The groups of Riksen, Joosten and Netea investigated the induction of trained immunity (innate immune memory) and the role of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Trained immunity is the key mechanism studied in REPROGRAM and proposed as a common diseases mechanism underlying atherosclerosis and rheumatoid arthritis.
The study published in CELL METABOLISM concluded that b-glucan-induced trained immunity in monocytes induces profound changes in cellular metabolism. The three most prominent metabolic pathways involved in trained immunity are glycolysis, glutaminolysis, and cholesterol synthesis, which are linked to enrichment in H3K4me3 that is essential for trained immunity by b-glucan. Finally, proof-of-principle of metabolo-epigenomic circuits is shown in innate immune memory by demonstrating an essential role for fumarate in modulating HIF1a degradation, histone methylation, and acetylation. The identification of the metabolic pathways contributing to induction of trained immunity improves understanding of innate immune memory and opens new therapeutic avenues.