Gene Regulatory Networks in Innate Immunity: From Immune Cell Plasticity to Chronic Inflammation

About the lecture

Gene Regulatory Networks in Innate Immunity: From Immune Cell Plasticity to Chronic Inflammation

 Institute for Genetics, Faculty of Mathematics and Natural Sciences, Cologne Excellence Cluster for Aging and Aging-Associated Diseases (CECAD), Cologne, Germany

Innate immune cells of the myeloid lineage are essential for organismal development, tissue homeostasis, and host defense. These cells exhibit remarkable plasticity, allowing them to rapidly adjust their activation states in response to diverse environmental and pathogenic signals. While this adaptability is vital for effective host defense and tissue repair, dysregulation of the underlying gene regulatory networks can lead to compromised immune responses, chronic inflammation, autoimmunity, immunosenescence, and age-associated pathologies.

At the Uhlirova laboratory, we investigate how innate immune cells interpret a variety of environmental cues and translate these signals into specific biological responses. Our research focuses on gene regulatory mechanisms, including transcriptional control and pre-mRNA splicing, that shape these responses. By leveraging the complementary strengths of both Drosophila melanogaster and mouse models, we explore conserved and species-specific mechanisms governing hematopoiesis, as well as immune cell differentiation, activation, and plasticity.

Our aim is to elucidate how gene regulatory circuits modulate immune cell behavior, including their interactions with tissue microenvironments and the inherent trade-offs of immune activation. Recent efforts focus on the role of innate immune cells in chronic inflammatory conditions characterized by granuloma formation, including foreign body reactions, as exemplified by responses to implanted biomaterials. Beyond their clinical significance, foreign body reactions represent a compelling biological paradigm for studying how innate immune cells sense and adapt to persistent environmental challenges, interact with their microenvironment, and drive the establishment of chronic inflammatory states. Insights from these studies may reveal fundamental principles of immune regulation as well as new therapeutic opportunities for inflammatory and age-related diseases.