Skin barrier dysfunction and systemic sensitization to allergens through the skin.
Most allergic, atopic and hypersensitive reactions are associated with Th2-biased immune responses and allergen-specific IgE antibodies. Pathological allergic disorders are on an alarming increase in the industrialized world. Understanding the mechanism of primary sensitization to allergens is important in elucidating the pathogenesis of these diseases and for possibly preventing their development. In this article, we review recent information supporting that epidermal allergen exposure may contribute to systemic allergic diseases and that atopy may be secondary to skin barrier dysfunction in some dermatoses. The skin is an active immunological organ, which functions as a primary defence and biosensor to the external environment. The critical permeability barrier function is mediated by the outmost layer of the epidermis, the stratum corneum. Perturbation of the stratum corneum initiates a chain of event, which activates homeostatic responses in the underlying epidermis. Repeated barrier-disruption, whether environmentally or genetically determined, may however stimulate signaling cascades that lead to inflammation and epidermal hyperplasia. Skin barrier dysfunction may also allow entry of allergens, which can lead to primary systemic sensitization. The altered epidermal microenvironment in barrier-disrupted skin appears to be particularly well suited for the induction of potent Th2-type responses with production of allergen-specific IgE. Epidermal exposure to food antigens can prevent the normal induction of oral tolerance and also lead to airway eosinophilia following inhalation. Exposure to allergens on barrier-disrupted skin may as such serve as a natural sensitization pathway for food allergy and respiratory allergic disease.
Strid
Jessica
J
Immunobiology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK. j.strid@ich.ucl.ac.uk
Strobel
Stephan
S
D000485:Allergens / Q000276:immunology*; D000818:Animals; D003876:Dermatitis, Atopic / Q000209:etiology; D004817:Epidermis / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000517:prevention & control; D007108:Immune Tolerance; D007801:Langerhans Cells / Q000378:metabolism; D008019:Life Style; D012867:Skin / Q000276:immunology / Q000378:metabolism*
D000485:Allergens