Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions.

Abstract:

:The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic DNA has been identified as a danger signal that activates inflammasomes 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 induced AIM2, and cytosolic DNA triggered the release of IL-1β via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptide LL-37, which can interact with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasome activation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern that can trigger 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 skin disease.

journal_name

Sci Transl Med

authors

Dombrowski Y,Peric M,Koglin S,Kammerbauer C,Göss C,Anz D,Simanski M,Gläser R,Harder J,Hornung V,Gallo RL,Ruzicka T,Besch R,Schauber J

doi

10.1126/scitranslmed.3002001

subject

Has Abstract

pub_date

2011-05-11 00:00:00

pages

82ra38

issue

82

eissn

1946-6234

issn

1946-6242

pii

3/82/82ra38

journal_volume

3

pub_type

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