Vascular Endothelial Cells and Innate Immunity

Abstract

In addition to the roles of endothelial cells (ECs) in physiological processes, ECs actively participate in both innate and adaptive immune responses. We previously reported that, in comparison to macrophages, a prototypic innate immune cell type, ECs have many innate immune functions that macrophages carry out, 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. In this highlight, we introduce recent advances published in both ATVB and many other journals: (1) several significant characters classify ECs as novel immune cells not only in infections and allograft transplantation but also in metabolic diseases; (2) several new receptor systems including conditional danger-associated molecular pattern receptors, nonpattern receptors, and homeostasis associated molecular patterns receptors contribute to innate immune functions of ECs; (3) immunometabolism and innate immune memory determine the innate immune functions of ECs; (4) a great induction of the immune checkpoint receptors in ECs during inflammations suggests the immune tolerogenic functions of ECs; and (5) association of immune checkpoint inhibitors with cardiovascular adverse events and cardio-oncology indicates the potential contributions of ECs as innate immune cells.

Interleukin 35 Delays Hindlimb Ischemia-Induced Angiogenesis Through Regulating ROS-Extracellular Matrix but Spares Later Regenerative Angiogenesis

“…In chronic inflammation, the formation of new blood vessels results in an increased endothelial surface area, which further facilitates inflammatory cell migration ( 18 ) into the inflamed tissue through vasodilatation and increased endothelial cell permeability ( 19 ). Although ECs are the most important cell types ( 20 ) in the angiogenic process, immune cell infiltration is critical for angiogenesis in the early stage of ischemia; although sustained inflammation can also lead to delayed angiogenesis ( 21 ) or undesired vessel overgrowth ( 22 ). Hindlimb ischemia represents a complex model with ischemia-induced necrosis and inflammation, ischemia-induced angiogenesis, arteriogenesis and skeletal muscle regeneration ( 23 ).…”

Approaching Inflammation Paradoxes—Proinflammatory Cytokine Blockages Induce Inflammatory Regulators

“…Indeed, in addition to PC regulation of IGs transcription examined in our study, PCs could also regulate innate immune regulators in several other modes: 1) mRNA stability (81); 2) riboclustering (82); 3) alternative splicing (83); 4) microRNA regulation (84); 5) long non-coding RNA regulation (85); 6) circular RNAs regulation (86); 7) protein translation (87); 8) protein neddylation (88); 9) ubiquitination-proteasome regulation (89); 10) epigenetic regulation (90); and 11) immune metabolism and innate immune memory (91,92). The proof of principles demonstrated in examination of inflammatory paradoxes performed in the current manuscript are far-reaching and can be extended to other fields of study such as cancers, infectious diseases such as COVID-19 and various pathologies.…”

How could we forget immunometabolism in SARS-CoV2 infection or COVID-19?

“…Vascular endothelial cells (VECs) lining the blood vessels form the vascular endothelium and also serve as innate immune cells [93,94]. The endothelial damage is responsible for vascular leakage and profound neutrophil and monocyte/macrophage infiltration in the inflamed and infected organ, including severe COVID-19 [94][95][96].…”

“…Vascular endothelial cells (VECs) lining the blood vessels form the vascular endothelium and also serve as innate immune cells [93,94]. The endothelial damage is responsible for vascular leakage and profound neutrophil and monocyte/macrophage infiltration in the inflamed and infected organ, including severe COVID-19 [94][95][96]. Endothelial cells also express the ACE2 receptor responsible for SARS-CoV2 entry in the cells, and COVID-19 patients show endothelial cell infection and endotheliitis (endothelial inflammation), it causes serious organ damage in severe COVID-19 patients, or it increases the severity of the COVID-19 [97,98].…”

“…Human endothelial cells express different cytosolic PRRs, including TLR3, TLR7, and TLR9, but they do not express TLR8, cGAS-STING, and RLRs [94,[168][169][170][171]. However, due to inhibition of TBK1 and other signaling molecules involved in type 1 IFN by the viral Nsp13 in infected endothelial cells only proinflammatory immune response (cytokines, ROS, and chemokines) is generated, therefore the virus keeps on growing, and the infected endothelial cells die due to apoptosis [96].…”