Research ArticlePsoriasis

Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions

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Science Translational Medicine  11 May 2011:
Vol. 3, Issue 82, pp. 82ra38
DOI: 10.1126/scitranslmed.3002001

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Taking AIM at Psoriasis

Everyday life is filled with dangers—from road construction and wet floors to biohazards and radiation. Warning signs, whether the ubiquitous ‘!’ or the classic skull and crossbones, signal impending peril, giving us the chance to change our course of action to avoid the hazards. Cells in the body also respond to danger signals, such as cytosolic DNA, which warns of microbial presence, activating inflammasomes that ramp up the body’s inflammatory response to damage. Now, Dombrowski et al. implicate cytosolic DNA in the inflammation associated with psoriasis, an autoimmune skin disease, and suggest how vitamin D may be able to counteract this response.

Psoriasis is a chronic inflammatory disease that commonly causes red, itchy plaques on the skin. Dombrowski et al. inspected both psoriatic and healthy human skin and found higher amounts of cytosolic DNA and AIM2—a DNA sensor associated with inflammasomes—in psoriatic keratinocytes, the predominant cell type in skin. Cytosolic DNA activated AIM2 inflammasomes in keratinocytes, which resulted in the production of proinflammatory cytokines. Importantly, the authors found that the cathelicidin peptide LL-37, which has antimicrobial function, also served as an anti-inflammatory agent by blocking activation of the DNA-sensing inflammasomes. Vitamin D controls cathelicidin production in human skin, and both topical vitamin D treatment and ultraviolet (UV) B light, which up-regulates vitamin D, are currently used to treat psoriasis. The new data from Dombrowski et al. not only provide a mechanistic explanation for the success of these therapies but also suggest that cathelicidin may constitute a new target that specifically affects the inflammasome. For psoriasis, the danger signal itself may be the hazard, and cathelicidin could be a means of defense.

Footnotes

  • * These authors contributed equally to this work.

  • Citation: Y. Dombrowski, M. Peric, S. Koglin, C. Kammerbauer, C. Göß, D. Anz, M. Simanski, R. Gläser, J. Harder, V. Hornung, R. L. Gallo, T. Ruzicka, R. Besch, J. Schauber, Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions. Sci. Transl. Med. 3, 82ra38 (2011).

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