Th2 Cytokines and Atopic Dermatitis

Abstract

Atopic dermatitis (AD), a chronic relapsing inflammatory skin disease, is increasing in prevalence around the world. Intensive research is ongoing to understand the mechanisms involved in the development of AD and offer new treatment options for patients suffering from AD. In this review, we highlight the importance of allergic Th2 responses in the development of the disease and summarize relevant literature, including genetic studies, studies of human skin and mechanistic studies on keratinocytes and mouse models of AD. We discuss the importance of the skin barrier and review recent findings on the pro-Th2 cytokines TSLP, IL-25, and IL-33, notably their ability to polarize dendritic cells and promote Th2 responses. After a brief update on the contribution of different T-cell subsets to AD, we focus on Th2 cells and the respective contributions of each of the Th2 cytokines (IL-4, IL-13, IL-5, IL-31, and IL-10) to AD. We conclude with a brief discussion of the current gaps in our knowledge and technical limitations.

Figure 1

Schematic representation of Th2 cytokines in AD. Keratinocytes are activated upon exposure to allergens, bacterial proteins or mechanical injury. A defective epidermal barrier caused by decreased expression or production of non-functional barrier proteins are in important contributing factor. Activated keratinocytes then secrete TSLP, IL-25, and IL-33 that then act on mast cells and antigen presenting cells (dendritic cells or Langerhans cells (LC)). Activated mast cells secrete numerous cytokines, several of which are Th2 cytokines. The dendritic cells then trigger Th2 polarization and secretion of IL-4, IL-5, IL-13, IL-31, and IL-10. The Th2 cytokines have both unique and overlapping functions including increased epidermal thickening, sensitization, inflammation, pruritus, decreased expression of antimicrobial peptides (AMPs), and the barrier proteins filaggrin (FLG), loricrin (LOR) and involucrin (INV). The role of IL-10 in AD, particularly its induction of inflammation remains controversial.