西亚试剂：Cytosolic DNA Triggers Inflammasome Activation in Keratinoc

Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions

Dombrowski, Yvonne; Peric, Mark; Koglin, Sarah; Kammerbauer, Claudia; G??, Christine; Anz, David; Simanski, Maren; Gl?ser, Regine; Harder, Jürgen; Hornung, Veit; Gallo, Richard L.; Ruzicka, Thomas; Besch, Robert; Schauber, Jürgen

The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatoryskin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanismstriggering IL-1β processing remain unknown. Recently, cytosolic DNA has been identified as a danger signal that activatesinflammasomes containing the DNA sensor AIM2. In this study, we detected abundant cytosolic DNA and increased AIM2 expression in keratinocytes in psoriatic lesions but not in healthy skin. In cultured keratinocytes, interferon-γ inducedAIM2, and cytosolic DNA triggered the release of IL-1β via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptideLL-37, which can interact with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasomeactivation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern that cantrigger AIM2 inflammasome and IL-1β activation in psoriasis. Furthermore, cathelicidin LL-37 interfered with DNA-sensing inflammasomes,which thereby suggests an anti-inflammatory function for this peptide. Thus, our data reveal a link between the AIM2 inflammasome,cathelicidin LL-37, and autoinflammation in psoriasis, providing new potential targets for the treatment of this chronic skindisease.