Current evidence of epidermal barrier dysfunction and thymic stromal lymphopoietin in the atopic march

Abstract

It has long been observed that the development of asthma, allergic rhinitis and food allergy are frequently preceded by atopic dermatitis, a phenomenon known as the "atopic march". Clinical, genetic and experimental studies have supported the fact that atopic dermatitis could be the initial step of the atopic march, leading to the subsequent development of other atopic diseases. This brief review will focus on the current evidence showing that epidermal barrier dysfunction and the keratinocyte-derived cytokine thymic stromal lymphopoietin play critical roles in the onset of the atopic march.

Figure 1.

Schematic representation of evidence from experimental mouse model studies showing how skin-derived cytokine thymic stromal lymphopoietin (TSLP) may contribute to the pathogenesis of atopic dermatitis, and the progression from atopic dermatitis to asthma: the so-called “atopic march”. Epicutaneous sensitisation to allergen may occur in skin that has epidermal barrier defects, due to either intrinsic genetic mutations of barrier genes (e.g. serine peptidase inhibitor, kazal type 5 (SPINK5), corneodesmosin (CDSN) and filaggrin (FLG)) and/or extrinsic stimuli. The cytokine TSLP, which is produced by skin keratinocytes (A), is crucially required for generating allergic skin inflammation and developing epicutaneous sensitisation to allergens (B). Furthermore, the overproduced TSLP, which can be induced and amplified by a variety of factors, boosts epicutaneous sensitisation (C), thereby promoting the atopic march. In addition, the skin-derived TSLP enters the circulation and can enhance the airway sensitisation to aeroallergens, such as house dust mites (D), thus aggravating the allergic asthma.