Analysis of the Mechanism for the Development of Allergic Skin Inflammation and the Application for Its Treatment: Keratinocytes in Atopic Dermatitis — Their Pathogenic Involvement

Abstract

Abstract. Atopic dermatitis frequently accompanies bronchial asthma, allergic rhinitis, and allergic conjunctivitis, the pathogenesis of which has frequently focused on the immunological aspects; however, skin eruption in atopic dermatitis occurs mainly in the epidermis, whose barrier function and cytokine expression have been revealed to be abnormal. In addition, the epidermis contains Langerhans cells, antigen-presenting cells, which could be considered the sentinel of the immune system. Some atopic dermatitis patients have been revealed to have mutations or SNPs (single-nucleotide polymorphisms) in the filaggrin gene, which affect the epidermal barrier function. Proteinases in the epidermis are of importance in maintaining the epidermal barrier, abnormalities of which have been reported in atopic dermatitis. Abnormalities of various cytokines and chemokines produced by keratinocytes have also been reported. Thymic stromal lymphopoietin (TSLP) produced by keratinocytes has recently been a focus in atopic dermatitis. Adrenergic/cholinergic responses in the epidermis could also influence the pathogenesis of atopic dermatitis. Considering epidermal keratinocytes as a trigger of immune abnormalities, not only as a peripheral effector, would be important to further disclose the pathogenesis of this enigmatic disorder.

The mechanism of atopic march may be the ‘social’ event of cells and molecules (Review)

“…More and more evidence is accumulating that the epithelial cells could be considered not only the frontier sentinels and barriers, but also the central participants in the innate and adaptive immune responses as well as in mucosal inflammation. The epithelial cells can release large quantities of proinflammatory cytokines, growth factors and chemokines that attract inflammatory cells to initiate and sustain an inflammatory reaction (28)(29)(30)(31)(32). The epithelial cells of the entire surface of the skin, the conjunctivae, the airways and the digestive tract are also the main targets during the pathogenesis of the systemic involvement of allergy (Fig.…”

“…Inflammation of the affected tissue is present in the epidermis and dermis where direct contact with the hapten takes place (34). Urticaria, angioedema, and AD are atopic disorders, in which contact of a specific allergen with the surface of the gastrointestinal or the respiratory tract drives an allergic reaction from the primary allergen contacted sites to the skin (30,34). Urticaria and angioedema are wheals, characterized by central swelling surrounded by erythema, associated with itching.…”

“…Urticaria and angioedema are wheals, characterized by central swelling surrounded by erythema, associated with itching. In the inflammatory process, both the dermis and the subcutis are involved, but the main target is the epidermis (30,34). AD is characterized by eczematous changes in the epidermis, and most patients have an atopic background with past or family histories of bronchial asthma, allergic rhinitis, and/or allergic conjunctivitis.…”

“…Infiltration of lymphoid cells into the epidermis and upper dermis can be observed under the microscope (34). The epidermal keratinocytes, which are triggers of immune abnormalities, as well as peripheral effectors, are important to further disclose the pathogenesis of this enigmatic disorder (29,30,34). Although the involved layer is different in individual cases of allergic skin diseases, the keratinocytes which produce cytokines and chemokines have been considered as the crucial factors in the initiation of skin inflammation (29,30,24).…”

Anti-Inflammatory Efficacy of Product Containing “Skin Calm Complex” <i>in Vitro</i> Reconstructed Epidermis

“…When the epithelial barrier functions are damaged, inflammatory events and sensitization processes IgE mediated occurs. So epidermis is not only a physical barrier, but also a chemical and immune barrier [15]. In addition, itch-scratch cycle exacerbates the epidemic barrier damage, increases water loss, dryness and inflammation, and favors pathogenic infections of the skin [1] [16].…”