An evolving new paradigm: endothelial cells--conditional innate immune cells

Abstract

Endothelial cells (ECs) are a heterogeneous population that fulfills many physiological processes. ECs also actively participate in both innate and adaptive immune responses. ECs are one of the first cell types to detect foreign pathogens and endogenous metabolite-related danger signals in the bloodstream, in which ECs function as danger signal sensors. Treatment with lipopolysaccharide activates ECs, causing the production of pro-inflammatory cytokines and chemokines, which amplify the immune response by recruiting immune cells. Thus, ECs function as immune/inflammation effectors and immune cell mobilizers. ECs also induce cytokine production by immune cells, in which ECs function as immune regulators either by activating or suppressing immune cell function. In addition, under certain conditions, ECs can serve as antigen presenting cells (antigen presenters) by expressing both MHC I and II molecules and presenting endothelial antigens to T cells. These facts along with the new concept of endothelial plasticity suggest that ECs are dynamic cells that respond to extracellular environmental changes and play a meaningful role in immune system function. Based on these novel EC functions, we propose a new paradigm that ECs are conditional innate immune cells. This paradigm provides a novel insight into the functions of ECs in inflammatory/immune pathologies.

Figure 1

Endothelial cells are conditional innate immune cells. In their quiescent state, endothelial cells express MHC I (Major histocompatibility class I) molecules and PPRs (pattern-recognition receptors) which detect PAMPs (pathogen-associated molecular patterns). In the presence of inflammatory stimuli and risk factors in the bloodstream, endothelial cells transform from an anti-inflammatory and anti-coagulatory state to a pro-inflammatory and pro-coagulatory state. Endothelial cells can detect inflammatory stimuli and risk factors via PRRs. In response to these stimuli, endothelial cells express MHC II molecules which present endothelial antigens to immune cells. Moreover, endothelial cells can upregulate the expression of surface adhesion molecules that induce the adhesion of immune cells, such as leukocytes, to the endothelium and facilitate transmigration to underlying tissues. In addition, endothelial cells enhance the secretion of pro-inflammatory cytokines and chemokines which can modulate the activities of immune cells.