A distinct metabolic and epigenetic state drives trained immunity in HSC-derived macrophages from autoimmune mice.

ABSTRACT: Here, we investigate the contribution of long-term hematopoietic stem cells (HSCs^LT) to trained immunity (TI) in the setting of chronic autoimmune disease. Using a mouse model of systemic lupus erythematosus (SLE), we show that bone marrow-derived macrophages (BMDMs) from autoimmune mice exhibit hallmark features of TI, including increased Mycobacterium avium killing and inflammatory cytokine production, which are mechanistically linked to increased glycolytic metabolism. We show that HSCs from autoimmune mice constitute a transplantable, long-term reservoir for macrophages that exhibit the functional properties of TI. However, these BMDMs exhibit reduced glycolytic activity and chromatin accessibility at metabolic genes while retaining elevated expression of TI-associated trans

SUBMITTER: Mills TS 

PROVIDER: S-EPMC11560650 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature