The role of filaggrin loss-of-function mutations in atopic dermatitis

Abstract

To provide a comprehensive summary of recent genetic advances as they relate to the pathogenesis of atopic dermatitis. Atopic dermatitis is a common inflammatory skin disease with a complex cause, resulting from an elaborate interplay between environmental, immunological and genetic factors. The disease is often the prelude to an atopic diathesis that includes asthma and other allergic diseases. The identification of mutations in the barrier protein filaggrin as conferring major susceptibility to atopic dermatitis and atopic dermatitis related asthma has reconfigured our understanding of disease mechanisms and highlights the importance of epidermal barrier disruption as a primary event in the disease. In this review we highlight recent advances in our understanding of how filaggrin might influence the environmental-immune interface, impacting disease penetrance, severity and trajectory, and the implications for both research and therapeutics in this field. Focusing on the downstream biological consequences of altered filaggrin expression and the sequence of immunological and environmental triggers that ensue will provide the rationale for targeted therapeutics capable of restoring or preventing disruption of barrier function.