Immune mechanisms of atopic dermatitis and new approaches to targeted biological therapy

Abstract

This review presents current data on immunopathogenesis, the role of cytokines in inflammation in atopic dermatitis (AD). The pathogenetic phenotypes of the disease associated with various abnormalities of immune mechanisms and dysfunction of the epidermal barrier are considered. The inflammatory processes in atopic dermatitis were shown to be implemented mainly through Th2-lymphocytes and IL-4 and IL-13 produced by these cells, which play a key role in the allergic cascade. It is the effects of IL-4 and IL-13 cytokines that determine the main pathophysiological mechanisms, such as decreased expression of epidermal barrier proteins and suppression of terminal differentiation of keratinocytes, microbiota disturbances, tissue remodelling, immunoglobulin isotype switching by B-lymphocytes and IgE synthesis, degranulation of mast cells and basophils, trafficking of inflammatory cells into tissues, itching. Moderate and severe forms of AD require administration of systemic therapy, which has been represented until recently by non-selective immunosuppressive drugs with moderate efficacy and pronounced side effects if they are used for a long time. Modern targeted therapy of atopic dermatitis provides for the use of monoclonal antibodies against both pro-inflammatory cytokines and their receptors. Directional action on the key mechanisms and targets of immune inflammation can minimize possible side effects of immunosuppressive therapy. Clinical trials on the efficacy and safety of IL-4 and IL-13 inhibitors in the treatment of atopic dermatitis are described.

Keywords

• atopic dermatitis
• cytokines
• targeted therapy
• dupilumab
• il-4
• il-13