Abstract
Pericytes (PC) are mural cells that surround endothelial cells in small blood vessels. PC have traditionally been credited with structural functions, being essential for vessel maturation and stabilization. However, an accumulating body of evidence suggests that PC also display immune properties. They can respond to a series of pro-inflammatory stimuli and are able to sense different types of danger due to their expression of functional pattern-recognition receptors, contributing to the onset of innate immune responses. In this context, PC not only secrete a variety of chemokines but also overexpress adhesion molecules such as ICAM-1 and VCAM-1 involved in the control of immune cell trafficking across vessel walls. In addition to their role in innate immunity, PC are involved in adaptive immunity. It has been reported that interaction with PC anergizes T cells, which is attributed, at least in part, to the expression of PD-L1. As components of the tumor microenvironment, PC can also modulate the antitumor immune response. However, their role is complex, and further studies will be required to better understand the crosstalk of PC with immune cells in order to consider them as potential therapeutic targets. In any case, PC will be looked at with new eyes by immunologists from now on.
Highlights
Pericytes (PC) were first described 145 years ago by Carl Joseph Eberth and “rediscovered” 2 years later by Charles-Marie Benjamin Rouget
PC of multiple origins have been reported to secrete a plethora of chemokines and cytokines in response to pro-inflammatory stimuli released by professional innate immune cells, mainly TNF-α, IL-1β, and IFN-γ (Table 1)
PC can respond to a series of pro-inflammatory stimuli and are able to discriminate between several types of danger and mount a complex secretory response: upon pathogen-associated molecular patterns (PAMPs) engagement, pattern- recognition receptors (PRR) trigger intracellular signaling cascades culminating in the expression of a variety of pro-inflammatory molecules
Summary
Pericytes (PC) were first described 145 years ago by Carl Joseph Eberth and “rediscovered” 2 years later by Charles-Marie Benjamin Rouget. Cells referred to as smooth muscle/PC have been shown to selectively induce the Ag-specific activation of different Th1 clones, reflected by cell proliferation and production of IL-2 [33] Some of these pioneering findings have been questioned as clear-cut identification of PC was not provided, and the results might rather be attributed to perivascular macrophages [34]. More recent studies have reported that isolated porcine brain PC do not express MHC class II molecules under basal conditions, but IFN-γ can induce its mRNA [36] and protein expression [37]. In a recent work, pretreatment with different stimuli, including IFN-γ, failed to induce an APC-like phenotype in human PC from various origins (placenta, brain, and CD146+, CD105+ pluripotent stem cell-derived). More studies are needed to establish the role of PC as macrophage-like cells, once unequivocal identification is warranted
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