Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously assumed. Accumulating evidence from experimental, genetic, and clinical studies indicates that AD expression is a precondition for the later development of other atopic diseases, such as asthma, food allergies, and allergic rhinitis. Although the exact mechanisms of the disease pathogenesis remain unclear, it is evident that both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of AD pathology. This review explores recent findings on AD and the possible underlying mechanisms involved in its pathogenesis, which is characterized by dysregulation of immunological and skin barrier integrity and function, supporting the idea that AD is a systemic disease. These findings provide further insights for therapeutic developments aiming to repair the skin barrier and decrease inflammation.

Keywords: atopic dermatitis; homeostasis; immunity; skin.

Figure 1

Skin barrier abnormalities and immune dysfunction are the main features of atopic dermatitis.

Figure 2

Schematic structure of the skin barrier and “brick and mortar” model.

Figure 3

Life cycle of filaggrin. Filaggrin exists as profilaggrin within keratohyaline granules in the granular layer of the epidermis. Profilaggrin is degraded to form filaggrin during the terminal differentiation process. Then, in the upper part of the stratum corneum (SC), filaggrin is degraded into amino acids and plays a crucial role in maintaining SC hydration and pH by forming natural moisturizing factors, including pyrrolidine carboxylic acid (PCA) and urocanic acid (UCA).

Figure 4

Thymic stromal lymphopoietin (TSLP) initiates the innate and adaptive phases of allergic immune responses in the skin. TSLP induces the maturation of dendritic cells to express OX40L, which in turn differentiates naive CD4+ T cells into Th2 cells to produce Th2 cytokines such as IL-4, IL-5, and IL-13, leading to the secretion of IgE from B cells. Together with the activation of Group 2 innate lymphoid cells (ILC2s), TSLP initiates the innate and adaptive immune responses of atopic dermatitis. Dieckol and phloxine O reduce atopic dermatitis-like inflammatory symptoms by inhibiting TSLP production.