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Atopic dermatitis (AD) is an inflammatory skin disease characterised by pruritus, dry skin, crusting and lichenification with a worldwide lifetime prevalence ranging from 1.8% to 44% across different populations.1 This disease poses significant medical, psychosocial and financial burdens for children and their families.2 AD has a complex aetiology that includes an impaired skin barrier, excessive type 2 T-helper lymphocyte (Th2) activity, reduced skin antimicrobial proteins and skin colonisation with Staphylococcus aureus.3 Filaggrin is a major structural protein in the stratum corneum (SC) of the epidermis and plays a critical role in maintaining the skin barrier function. The discovery that null mutations in the filaggrin gene (FLG) are associated with AD represented a significant breakthrough in the understanding of this complex disorder and the key role of skin barrier dysfunction in AD.4 Filaggrin mutations have reliably shown to be associated with the development of AD and remain an important paradigm for thinking about the pathophysiology of AD and subsequent allergies. Here, we review the central role of decreased filaggrin levels in the pathogenesis of AD, describe how filaggrin deficiency causes so-called ‘leaky skin’ and discuss promising strategies for AD treatment and prevention.
Role of filaggrin
The epidermis, specifically the SC, is the first-line defence between humans and the environment, including allergens, irritants and microbes. The SC is also responsible for minimising water loss from the body. The SC is composed of corneocyte cells surrounded by cell envelopes (CE) embedded in an intercellular lamellae. Sometimes, this is referred to as the ‘bricks’ and ‘mortar’ model of the skin barrier, and while not a perfect analogy, it captures the basic ideas nicely. Corneocytes (the ‘bricks’) are flattened, anucleate keratinocytes linked by protein bridges called corneodesmosomes. The CE is a tough, insoluble protein structure that replaces the plasma membrane in corneocytes. The …
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