Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases

Host defense peptides/proteins ( HDP s), also known as antimicrobial peptides/proteins ( AMP s), are key molecules in the cutaneous innate immune system. AMP s/ HDP s historically exhibit broad‐spectrum killing activity against bacteria, enveloped viruses, fungi and several parasites. Recently, AMP s/ HDP s were shown to have important biological functions, including inducing cell proliferation, migration and differentiation; regulating inflammatory responses; controlling the production of various cytokines/chemokines; promoting wound healing; and improving skin barrier function. Despite the fact that AMP s/ HDP s protect our body, several studies have hypothesized that these molecules actively contribute to the pathogenesis of various skin diseases. For example, AMP s/ HDP s play crucial roles in the pathological processes of psoriasis, atopic dermatitis, rosacea, acne vulgaris, systemic lupus erythematosus and systemic sclerosis. Thus, AMP s/ HDP s may be a double‐edged sword, promoting cutaneous immunity while simultaneously initiating the pathogenesis of some skin disorders. This review will describe the most common skin‐derived AMP s/ HDP s (defensins, cathelicidins, S100 proteins, ribonucleases and dermcidin) and discuss the biology and both the positive and negative aspects of these AMP s/ HDP s in skin inflammatory/infectious diseases. Understanding the regulation, functions and mechanisms of AMP s/ HDP s may offer new therapeutic opportunities in the treatment of various skin disorders.