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The Role of Host Defense Peptides in the Development and Pathogenesis of Psoriasis

Jürgen Schauber, MD

The production of antimicrobial peptides (AMPs) by resident and infiltrating cells is a primary defense system in cutaneous innate immunity. The β-defensins and the cathelicidins are two families of AMPs that protect the skin through distinct pathways: direct antimicrobial activity against an array of pathogens, and initiation of a host response that results in cytokine release and inflammation. The multiple roles of AMPs prompted their alternative designation as “alarmins”, and AMP dysregulation or dysfunction emerges as a central factor in the pathogenesis of several cutaneous diseases, including psoriasis. As an example, higher genomic copy numbers of β-defensin genes correlate with an increased risk of developing psoriasis. On a molecular level, cathelicidin peptide LL-37 converts self-DNA into a potent stimulus in an autoinflammatory cascade in psoriatic skin and triggers an interferon-α response. Expression of β-defensins and cathelicidin in the skin is regulated by distinct cytokines, as well as by vitamin D3. Therapies that target the control of β-defensins, cathelicidin, and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases. Adv Psor Inflam Skin Dis 2009;1(1):1–5.

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