Immune functions of vascular structural cells are endothelial communication, smooth muscle transdifferentiation and lymphatic immune regulation

The vascular wall maintains structural integrity, regulates blood flow, and supports tissue functions and homeostasis. Evidence also shows that its structural cells participate in immune sensing, inflammation and tissue remodeling. Vascular endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and lymphatic endothelial cells (LECs) encounter different combinations of inflammatory, metabolic, mechanical, microbial, tissue and intracellular immune-derived signals. We propose here that their anatomical locations and cell-intrinsic programs shape distinct, context-dependent immune functions of vascular structural cell types. ECs act as immune communicators at the blood-tissue interface. In response to inflammatory cues, they produce cytokines and chemokines, express adhesion molecules, regulate vascular permeability, and direct leukocyte recruitment. VSMCs respond to persistent vessel wall stress through phenotypic plasticity, secretomes and transdifferentiation, adopting cell states that may support repair and plaque stability or contribute to fibrosis, calcification, and disease progression. LECs combine innate sensing with regulation of immune cell trafficking, antigen handling, peripheral tolerance, adaptive immune responses, and fluid balance. Single-cell transcriptomic studies also identify immune-associated signatures in other vascular structural cell populations, including fibroblasts and pericytes. However, these populations remain candidates whose immune functions require spatial lineage-resolved and functional validation. Together, ECs, VSMCs, and LECs illustrate complementary ways in which structural cells contribute to vascular immune regulation. Defining the novel mechanisms and disease contexts of these responses may reveal opportunities to moderate vascular inflammation and remodeling for development of new disease therapeutics.