Revisiting endothelial biology: Immune sentinels of the vasculature in inflammation and disease

Endothelial cells (ECs), which line the inner surface of all blood vessels, are increasingly recognized not only as structural components of the vasculature but also as active regulators of immune surveillance, inflammation, and tissue homeostasis. Positioned at the interface between blood and tissues, ECs orchestrate leukocyte recruitment, antigen presentation-related functions, cytokine and chemokine signaling, vascular permeability, coagulation, and resolution of inflammation. Emerging evidence suggests that ECs adopt context-dependent immune phenotypes and share functional programs with innate and adaptive immune cells, highlighting their underappreciated role as immunomodulatory hubs in health and disease.Endothelial dysfunction is now understood as a central driver of chronic inflammation and immune-mediated pathology across a broad range of conditions, including autoimmune and autoinflammatory diseases, infection, sepsis, cancer, cardiometabolic disorders, and fibrotic disease. In these settings, ECs contribute to immune cell trafficking, vascular inflammation, immunothrombosis, tissue injury, and maladaptive repair. Despite their pivotal role in inflammatory disease mechanisms, endothelial-directed therapeutic approaches remain limited. A deeper understanding of how ECs integrate inflammatory cues, regulate immune responses, and shape tissue-specific disease microenvironments is therefore essential for identifying new therapeutic opportunities.This Research Topic aims to advance our understanding of endothelial cells as key players in inflammation and immunology, with particular emphasis on their roles in vascular immune regulation, inflammatory signaling, and disease pathogenesis. By bringing together studies on endothelial barrier disruption, leukocyte-endothelial interactions, immune signaling pathways, and endothelial heterogeneity, this collection seeks to define how ECs influence immune responses locally and systemically. The objective is to gather original research and authoritative reviews that address unresolved questions in endothelial immunobiology, characterize the molecular pathways linking EC dysfunction to inflammatory disease, and explore how these mechanisms may be therapeutically targeted to improve clinical outcomes.Within this focused framework, the Research Topic welcomes submissions addressing the molecular and cellular mechanisms by which endothelial cells regulate inflammation and immunity in health and disease, while excluding studies unrelated to endothelial biology or lacking a clear endothelial-centered perspective. Topics of interest include, but are not limited to:- Mechanisms regulating endothelial activation, barrier dysfunction, and vascular permeability during inflammation- Endothelial-immune cell crosstalk in innate and adaptive immune responses- Endothelial contributions to immunothrombosis, vascular inflammation, and inflammatory resolution- Endothelial dysfunction in autoimmune diseases, infection, sepsis, cancer, diabetes, and chronic inflammatory disorders- Angiocrine and inflammatory signaling pathways linking ECs to tissue injury, repair, and fibrosis- Translational and therapeutic strategies targeting endothelial-mediated inflammatory pathways Topic editors: Baharak Hosseinkhani, Maria Georgiadou Source: https://www.frontiersin.org/research-topics/81001/revisiting-endothelial-biology-immune-sentinels-of-the-vasculature-in-inflammation-and-disease