Review Article

Innate Immunity and Allergy in the Skin

MARTIN METZ AND MARCUS MAURER Allergie-Centrum-Charite , Department of Dermatology and Allergy, Charite Universita tsmedizin Berlin, Berlin, Germany Current Opinion in Immunology 2009, 21:687693

Introduction
The skin fulfils a multitude of different functions; for example, it is an important sensory organ, it contributes to hormone balance and the regulation of body temperature and is of major importance in social/sexual communication. The most important role of the skin may, however, be the protection against environmental threats such as microbes, UV light, or chemicals.

 Keratinocytes (KCs), dendritic cells (DCs), and mast cells (MCs), that is resident skin cells, all contribute in many ways to optimal innate defense mechanisms. KCs, DCs, and MCs have been implicated in allergic skin reactions, and DCs can process and present allergens to other cells of the immune system after the allergen has penetrated through the epithelial barrier, finally leading to the sensitization to the respective allergen. Contact with the allergen then results in the activation of MCs and the release of histamine which in turn leads to the development of immediate hypersensitivity type allergic reactions.

Dendritic Cells
If the epidermal barrier is disrupted, pathogens as well as allergens make contact with other resident innate immune cells in the skin. DCs are professional antigen-presenting cells, which are ideally located to detect any skin invading pathogen and allergen. DCs are a heterogeneous population of immune cells, which are thought to exert different functions depending on their origin, their state of activation and their location.

 The major function of DCs is the initiation of adaptive immune responses, for example the presentation of microbial antigens to T cells and the modulation of T cell differentiation. In the skin, Langerhans cells as well as dermal DCs can take up antigen, process it into fragments and migrate to regional lymph nodes where they present the antigen to cells of the adaptive immune system.

 Autocrine or paracrine activation of DCs or Langerhans cells by IL-1 is one of the suggested mechanisms leading to the control of bacterial skin infection. In addition to the recruitment of neutrophils, van Beelen and colleagues reported that DC-derived IL-1 and IL-23 are also involved in the promotion of IL-17 production in memory Th cells, which can contribute to the protection against certain bacteria.

Mast cells Allergy cells and Masters of Innate Immunity in the Skin
Functions of MCs, these are the cells responsible for allergies. The ability of MCs to release histamine in response to allergen-mediated crosslinking of specific IgE bound to FceRI expressed on their surface, which makes it, indeed, the most important cellular player in the induction of allergic symptoms. The role in allergic reactions may be far more complex and that they are critically involved in the defense against pathogens invading the skin.

Skin Mast Cells in Innate Immunity

The initial findings regarding the important role of MCs in innate immune responses are derived from models of bacterial infections in the peritoenum. Although there is increasing evidence that MCs can also contribute to host defense against viruses and fungi. MCs are equipped with very many different receptors expressed on their surface and activation of one or more of these receptors can result in the secretion of a wide array of biologically active mediators.

10

 In general, MCs are thought to be important cells in innate immune reactions because of the immediate response to a danger signal which results in the rapid release of substances that then control the respective danger. Therefore, the novel findings that MCs are also capable of modulating long term, and therefore potentially harmful, inflammatory skin reactions to environmental danger signals.

11

Mast cells in the skin-bridging allergy and innate immunity

The most striking interference between these systems is the exacerbation of allergic dermatitis by microorganisms such as bacteria and fungi. The skin commensal yeast Malassezia sympodialis for example was demonstrated to activate MCs and to enhance IgE-mediated MC degranulation, indicating that this may be a relevant factor for the exacerbation of the inflammatory response in atopic dermatitis. On the other hand, nonpathogenic commensal bacteria have been shown to be able to function as a strong, direct inhibitor of IgE-mediated MC degranulation in vitro and in vivo, offering potential new therapeutic alternatives for the treatment of allergies.
12

 These and other findings strongly support the hypothesis that skin MCs are able to specifically respond to certain environmental danger signals with a tailored response, that is upregulation or downregulation of specific MC functions or secretion of a specific subset of mediators.

13

 In response to various TLR ligands we were recently able to show that connective tissue-type MCs respond differentially with either a secretion of a more proinflammatory or modulatory set of cytokines [50] which may also have implications for the interactions with IgEmediated allergic reactions. One possible speculation is based on the finding that skin MCs are protective against the bites and stings of venomous animals.

14

Thank you

15