Antimicrobial peptides and the skin immune defense system

Our skin is constantly challenged by microbes but is rarely infected. Cutaneous production of antimicrobial peptides (AMPs) is a primary system for protection, and expression of some AMPs further increases in response to microbial invasion. Cathelicidins are unique AMPs that protect the skin through 2 distinct pathways: (1) direct antimicrobial activity and (2) initiation of a host response resulting in cytokine release, inflammation, angiogenesis, and reepithelialization. Cathelicidin dysfunction emerges as a central factor in the pathogenesis of several cutaneous diseases, including atopic dermatitis, in which cathelicidin is suppressed; rosacea, in which cathelicidin peptides are abnormally processed to forms that induce inflammation; and psoriasis, in which cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Recent work identified vitamin D3 as a major factor involved in the regulation of cathelicidin. Therapies targeting control of cathelicidin and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases.

Key words: Antimicrobial peptides, alarmins, skin, cathelicidin, rosacea, atopic dermatitis, psoriasis, 1,25 dihydroxy vitamin D3

Abbreviations used: AMP, Antimicrobial peptide, 1,25D3, 1,25 dihydroxy vitamin D3, 25D3, 25 hydroxy vitamin D3, pDC, Plasmacytoid dendritic cell, TLR, Toll-like receptor