Pellino‐2 and NLRP3 inflammasome activation in corneal disease

Abstract

Inflammation is a common factor in disease development of several corneal diseases. While a successful inflammatory response can clear an infection, eliminate a trigger, and repair tissue damage, it has also been shown that persistent antigenic stimulus, autoimmunity, long term exposure to irritants or a faulty inflammatory response can lead to chronic inflammation. The consequences of such chronic inflammation can be tissue damage, misdirected and incomplete wound repair, and can be accompanied by ingrowth of new blood vessels.Well‐regulated NLRP3 inflammasome activation has been shown to have protective effects against keratitis and corneal neovascularization. In contrast, abnormal activation of the NLRP3 inflammasome has been seen in acute glaucoma, age‐related macular degeneration, uveitis and Behcet's syndrome, as well as in hereditary, monogenic diseases, such as keratitis fugax hereditaria.A common trigger for NLRP3 inflammasome activation, upon treatment with various NLRP3 stimuli, is the efflux of cytosolic potassium (K+). We have recently shown that the E3 ubiquitin ligase Pellino‐2 changes intracellular localization following K+ efflux from immune cells and colocalizes with NLRP3 in activated macrophages, suggesting that Pellino‐2 is essential for mediating the effect of K+ efflux on NLRP3 inflammasome activation. Hyperactivation of the inflammasome has been linked to the formation of keloids as well as the development of corneal neovascularization.Here the implications of the NLRP3 inflammasome activation in innate immune cells will be discussed, and how an overactivated inflammasome contributes to corneal disease development.