Rewiring the bone marrow: Evolution and the transcriptional architecture of trained immunity
Year: 2025
Type: article
Abstract: The epigenetic adaptation of innate immune cells to inflammatory stimuli, or trained immunity, represents an evolutionarily conserved feature of host defense. Recent advances have revealed that such adaptations can occur at the level of hematopoietic stem and progenitor cells, resulting in long-lasting epigenetic reprogramming of the immune system. However, a comprehensive mechanistic understanding of these processes remains incomplete, limiting our capacity to predict or therapeutically manipulate the adaptive capacity of hematopoiesis. In this review, we survey the current literature to support a model of hematopoietic memory whose stimulus-specific nuances are shaped by specific cytokine environments and driven by the combinatorial activity of key transcription factors. Comparative analyses underscore the evolutionary conservation and essential biological roles of these factors, suggesting that trained immunity may reflect the strategic repurposing of ancient transcriptional programs for the purpose of enhancing host defense.
Source: eLife
DOI: 10.7554/elife.107551
Institutions: University of Chicago, Chan Zuckerberg Biohub Chicago
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G1051678693, G1212783069, G3605028095, G4681002531, G494116980, G5762917471, G7009275038, G7617432318, G7963069742, iPSC-derived macrophages as a model to study the genetic basis of inter-individual variation in immune responses to pathogens, Center for Interdisciplinary Study of Inflammatory Intestinal DIsorders (C-IID), Characterizing the genetic and evolutionary determinants of population variation in transcriptional responses to pathogens, Medical Scientist National Research Service Award, Unraveling the molecular mechanisms of innate immune memory in humans
OpenAlex ID: W4415532932