Lymphatic vessels are failing to drain fluid properly in conditions like lymphoedema, and a protein called ERG may hold the key to why. Lymphatic vessels do more than just drain excess fluid from tissues — they also shuttle immune cells to lymph nodes, where immune responses are coordinated. When these vessels malfunction, fluid builds up and immunity can be compromised. Researchers know that ERG helps regulate the inner lining of blood vessels, but its role in the lymphatic system is poorly understood. This project aims to clarify how ERG controls lymphatic vessel identity and immune function at the molecular level. If successful, this fundamental science will map the specific genetic pathways that go awry in lymphatic dysfunction. That map could eventually guide the development of drugs that restore lymphatic drainage or modulate immune trafficking — potentially improving treatment for lymphoedema and other conditions where immune responses need to be boosted or calmed. For now, the work is curiosity-driven, but understanding how a master regulator like ERG shapes lymphatic behaviour is a necessary first step before any therapeutic application becomes possible.
View original technical description
Lymphatic vessels represent an essential component of the circulatory system, where they operate intimately with the blood vasculature to mop-up fluid and blood capillary exudates from interstitial tissue spaces, maintaining fluid and tissue homeostasis. The resulting protein-rich lymph travels along a lymphatic vessel hierarchy punctuated by lymph nodes (LN) before returning to the circulation. Lymphatic dysfunction leads to disturbed tissue fluid balance and lymphoedema. Lymphatics are also emerging as gatekeepers of immunity thanks to their intimate connection to LN immune hubs, providing a continual source of antigen, supporting rapid immune cell mobilization, generating chemotactic gradients and expressing a repertoire of adhesion molecules to facilitate immune trafficking, and scavenging antigen. Although endothelial cells (ECs) lining both blood and lymphatic vessels share common molecular and cellular processes, there is extensive specialisation underlying the unique functions of these two vascular systems. These differences reflect specific transcriptional programs, that can be regulated by transcription actors, including members of the ETS, FOX and SOX families. ERG is one of the most highly expressed ETS transcription factors in blood ECs, serving as a master regulator of endothelial homeostasis. ERG deficiency is embryonically lethal due to catastrophic vascular defects. Our ongoing work has highlighted a unique role for ERG in regulating lymphatic endothelial cell (LEC) gene programs, and in regulating lymphangiogenesis. While ERG is emerging as a key endothelial transcriptional regulator of both blood and lymphatic endothelium, how its expression contributes to lymphatic identity and immune functionality essential for generation of immune responses remains unclear. Here we will employ functional assays with high resolution transcriptomics and imaging to address this, gaining valuable insights into the molecular mechanisms underlying lymphatic function and dysfunction in pathologies such as lymphoedema. Identifying pathways that play pivotal roles in the breakdown of lymphatic immune function provides a roadmap for potential therapeutic targets to modulate immunity for patient benefit.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know