Immunomodulation by endothelial cells — partnering up with the immune system?

Abstract

Blood vessel endothelial cells (ECs) have long been known to modulate inflammation by regulating immune cell trafficking, activation status and function. However, whether the heterogeneous EC populations in various tissues and organs differ in their immunomodulatory capacity has received insufficient attention, certainly with regard to considering them for alternative immunotherapy. Recent single-cell studies have identified specific EC subtypes that express gene signatures indicative of phagocytosis or scavenging, antigen presentation and immune cell recruitment. Here we discuss emerging evidence suggesting a tissue-specific and vessel type-specific immunomodulatory role for distinct subtypes of ECs, here collectively referred to as ‘immunomodulatory ECs’ (IMECs). We propose that IMECs have more important functions in immunity than previously recognized, and suggest that these might be considered as targets for new immunotherapeutic approaches.

Mucosal immune responses to infection and vaccination in the respiratory tract

“…However, numerous studies have shown that these cells may play a more direct role in tolerance, immune surveillance (scavenging), active phagocytosis, immune cell recruitment from the periphery, and antigen presentation to conventional (CD4/CD8) and unconventional (iNKT) T cells. Collectively, these EC subsets are referred to as immunomodulatory endothelial cells (IMECs), and their numerous unique functions have been detailed elsewhere ( Amersfoort et al., 2022 ). However, evidence for detrimental functions during antiviral response have also been uncovered.…”

Childhood Immunity and Infections: Time to Consider Endothelial Cells and Platelets

“…Recent interesting studies also demonstrated that ECs have many innate immune functions and express gene signatures indicative of phagocytosis or scavenging, antigen presentation, and immune cell recruitment [ 14 ]. Specifically, they have functions that macrophages express, including cytokine secretion, phagocytic function, antigen presentation, pathogen-associated molecular patterns-, and danger-associated molecular patterns-sensing, proinflammatory, immune-enhancing, anti-inflammatory, immunosuppression, migration, heterogeneity, and plasticity [ 11 ].…”

“…Moreover, ECs behave as innate immune cells also in metabolic cardiovascular diseases, other sterile inflammations, and cancers. These concepts are extremely relevant in the case of chronic inflammatory states, which have a known role in cancerogenesis [ 14 ].…”

“…Jacob Amersfoort and colleagues also proposed and an immunomodulatory function of ECs: in the lung and liver they mediate the balance between tolerance and inflammation, in the kidney and liver they closely interact with resident immune cells, in the brain, they form a tight and low immunomodulatory barrier to minimize infiltration of the tissue parenchyma [ 14 ].…”

Transcriptomic and Functional Evidence for Differential Effects of MCF-7 Breast Cancer Cell-Secretome on Vascular and Lymphatic Endothelial Cell Growth

“…The lymphatic vessels serve as a conduit to channel immune cells to counteract cancer cell growth [19]. Indeed, crosstalk between lymphatic and immune cells plays an important role in the uptake/migration of cells into the lymphatics [20] via LEC-generated chemokine(s) gradients [21].…”