Endothelial cells: From innocent bystanders to active participants in immune responses

•Endothelial cells contribute to inflammation via angiogenesis and attraction of immune cells.•Endothelial cells also have immunoregulatory functions and may play a role in antigen presentation.•Under specific conditions, endothelial cells may acquire mesenchymal features (EndMT).•Targeting of endothelial cells may be beneficial in chronic inflammatory diseases.

The endothelium is crucially important for the delivery of oxygen and nutrients throughout the body under homeostatic conditions. However, it also contributes to pathology, including the initiation and perpetuation of inflammation. Understanding the function of endothelial cells (ECs) in inflammatory diseases and molecular mechanisms involved may lead to novel approaches to dampen inflammation and restore homeostasis. In this article, we discuss the various functions of ECs in inflammation with a focus on pathological angiogenesis, attraction of immune cells, antigen presentation, immunoregulatory properties and endothelial-to-mesenchymal transition (EndMT). We also review the current literature on approaches to target these processes in ECs to modulate immune responses and advance anti-inflammatory therapies.