Abstract
During induction of trained immunity, monocytes and macrophages undergo a functional and transcriptional reprogramming toward increased activation. Important rewiring of cellular metabolism of the myeloid cells takes place during induction of trained immunity, including a shift toward glycolysis induced through the mTOR pathway, as well as glutaminolysis and cholesterol synthesis. Subsequently, this leads to modulation of the function of epigenetic enzymes, resulting in important changes in chromatin architecture that enables increased gene transcription. However, in addition to the beneficial effects of trained immunity as a host defense mechanism, we hypothesize that trained immunity also plays a deleterious role in the induction and/or maintenance of autoimmune and autoinflammatory diseases if inappropriately activated.
Highlights
Since the introduction of the term trained immunity for the non-specific memory of the innate immune system in 2011 [1], an increasing number of studies have investigated its role in homeostasis and disease
We have recently shown that the induction of trained immunity by β-glucan is able to counteract the epigenetic changes induced in monocytes in postsepsis immunoparalysis [18]: this may represent a potential new therapy
When peripheral blood monocytes from recent-onset TYPE 1 DIABETES MELLITUS (T1DM) patients were assessed, more CD14+CD16+ monocytes were found, which was negatively correlated with insulin and C-peptide serum levels
Summary
Role of Trained Immunity in Autoimmune and Autoinflammatory Disorders. During induction of trained immunity, monocytes and macrophages undergo a functional and transcriptional reprogramming toward increased activation. Important rewiring of cellular metabolism of the myeloid cells takes place during induction of trained immunity, including a shift toward glycolysis induced through the mTOR pathway, as well as glutaminolysis and cholesterol synthesis. This leads to modulation of the function of epigenetic enzymes, resulting in important changes in chromatin architecture that enables increased gene transcription.
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