Innate Immunity in the Skin

Abstract

out to be crucial for many inflammatory processes cen-trally involved in dermatological diseases. In the first review of this issue, de Koning et al. [1] summarize the current knowledge on pattern recogni-tion receptors in immune disorders affecting the skin. They show that pattern recognition receptors like Toll-like receptors and members of the leucine-rich repeat-domain proteins participate in common cutaneous in-flammatory diseases like psoriasis, atopic dermatitis and allergic contact dermatitis. Most has been learned from very rare diseases, which are monogenetic in their in-heritance, like cryopyrin-associated periodic syndrome, NLRP12-associated periodic syndrome and Blau’s syn-drome, which are all caused by specific defects in the in-flammasome complex. This understanding has already changed the therapeutic approach in these patients, which are nowadays excellently treated by IL-1 antago-nists. Due to this therapeutic breakthrough, there were great expectations for novel drugs targeting pattern rec-ognition receptors and their specific pathways.T he other two papers in this issue deal with antimicro-bial peptides, which are the effector molecules of the in-nate immune system. In their review, Simanski et al. [2] discuss the role of antimicrobial RNases in cutaneous de-fense mechanisms. RNase 7, for example, is a highly ac-tive antimicrobial peptide expressed in healthy human skin [3]. I n contrast to other antimicrobial peptides, it has not attracted the same attention as defensins for instance, though its antimicrobial capacity and its expression in the human skin is comparable and even higher compared L ooking at the skin might evoke different associations and emotions among different spectators. The beauty of nature led some sometimes to forget the efficient and complex immunological organ in front of us. The skin protects us not only from water loss and physical damage, it is also our protective shield against microorganismswe have to face in this world. However, skin infections rarely occur. To combat microbial attacks, an efficient immune system is needed. It acts at different levels de-pending on how many resources are required to stay healthy – nature is not only beautiful but also economic. These different defense levels go hand in hand and com-plement each other. First of all, the skin possesses a repertoire of antimi-crobial substances on its surface. They are derived from keratinocytes and prebuilt during the differentiation process to fight surrounding microbes. The underlying epidermis functions not only as a ‘bricks-and-mortar’ barrier but also as a sensor to environmental hazards. Keratinocytes and epidermal dendritic cells (Langerhans cells) express different receptors to sense dangerous mol-ecules. These innate immune receptors, some being lo-cated on the cell surface and others within the cell, initi-ate immune responses. These immune responses range from enhancement of antimicrobial activity by inducing antimicrobial production over the release of inflamma-tory cytokines to antigen presentation and control of adaptive immune responses. Research during recent years has revealed that this innate immune system is not involved in the direct fight against pathogens but turns