Keratinocytes express functional CARD18, a negative regulator of inflammasome activation, and its altered expression in psoriasis may contribute to disease pathogenesis

The caspase-1 inhibitor CARD18 is specifically expressed during late differentiation of keratinocytes and its expression is lost in lichen planus

“…Here, we first characterized the expression profile of CARD18 in different human tissues and analyzed its potential contribution to the formation of the skin barrier. Our data that CARD18 is induced during terminal differentiation of keratinocytes in vitro are in agreement with the published results of CARD18 mRNA quantification in keratinocytes undergoing differentiation in vitro [17]. However, Göblös et al [17] reported uniform immunolabeling of CARD18 protein in all layers of the epidermis, which would not fit to differentiationassociated expression of CARD18.…”

“…During the preparation of this manuscript, Göblös and coworkers reported that CARD18 is expressed in all layers of normal human epidermis and that its expression levels are increased in psoriasis [17]. Suppression of CARD18 expression enhanced the secretion of IL-1b from cultured keratinocytes in response to poly (dA:dT) treatment [17], indicating that CARD18 might reduce the activation of caspase-1 by the cytosolic DNA-responsive AIM2 inflammasome. Here, we utilized a new antibody against CARD18 and re-defined the in situ expression profile of CARD18 by demonstrating specific localization to the granular epidermal layer and the stratum corneum in normal human skin.…”

High‐fat diet exacerbates imiquimod‐induced psoriasis‐like dermatitis in mice

“…Keratinocytes are candidate to activate inflammasomes. HMGB1, one of the DAMPs, and its downstream cytokine IL‐18 in keratinocytes contributed to the development of psoriasiform dermatitis in IMQ‐treated mice and psoriasis‐associated danger signals increased the production of IL‐1β by keratinocytes . Consequently, HFD may activate inflammasomes in the keratinocytes of IMQ‐treated mice, affecting the severity of psoriasiform dermatitis.…”

Immunpathogenesis and genetics of skin diseases

“…Negatív szabályozó molekulákat (TNIP1, TNFAIP3) is azonosítottunk, melyek a C. acnes kiváltotta immunaktiváció kontrollálásában vehetnek részt. A TNIP1 molekula esetében igazoltuk, hogy az acne terápiájában használt retinoidok ezen molekula szintjének szabályozásával, a veleszületett immunfolyamatok közvetlen gátlása révén is kifejtik hatásukat (13) A pikkelysömör patogenezise során specifikus multiprotein komplexek, úgynevezett inflammaszómák aktivációja is bekövetkezik, mely folyamatok szabályozásában az általunk azonosított CARD18 molekula játszik központi szerepet (24).…”