Building Giant Cells: Transcriptional Control of Macrophage Fusion

Le 25 septembre 2026 à 08h00 Séminaire

During development and throughout life, multicellular organisms depend on tightly coordinated gene expression. Selective activation and repression of genes are required not only to generate the many specialized cell types that constitute a functional organism, but also to allow cells to sense and respond to changing environmental cues. Innate immune cells exemplify this plasticity, adapting to combat pathogens and eliminate damaged or aberrant cells while preserving tissue function and organismal integrity.

In the Uhlirova laboratory, we investigate how innate immune cells interpret environmental cues and translate them into specific biological responses. Using the complementary strengths of Drosophila melanogaster and mouse models, we study conserved and species-specific gene-regulatory mechanisms, including transcriptional control and pre-mRNA splicing, that govern hematopoiesis and immune-cell differentiation, activation, and plasticity. Our goal is to understand how these regulatory circuits shape immune cell behavior, their interactions with tissue microenvironments, and the inherent trade-offs of immune activation.

In this talk, I will present our identification of the stress-responsive transcription factor ATF3 as a central regulator of macrophage adaptation to chronic IL-4 signaling during foreign-body reactions. I will show how ATF3 coordinates lipid homeostasis, cytoskeletal remodeling, and nuclear integrity to drive multinucleated giant-cell formation via cell-cell fusion, and discuss how multinucleation reshapes macrophage function. Together, findings reveal how gene regulation links cellular metabolism and architecture to control macrophage plasticity under chronic inflammatory conditions.