Cytokine modulation of atopic dermatitis filaggrin skin expression

Abstract

The atopic immune response contributes to the skin barrier defect in AD; therefore, neutralization of IL-4 and IL-13 could improve skin barrier integrity.

New insights in the pathogenesis of atopic dermatitis

“…IL-4 and IL-13 produced by Th2 have been shown to suppress filaggrin expression by keratinocytes (42). This is consistent with the clinical observation that filaggrin expression is significantly lower in the lesional AD, as compared to nonlesional AD skin (43).…”

Filaggrin Genotype in Ichthyosis Vulgaris Predicts Abnormalities in Epidermal Structure and Function

“…Disruption of the epidermal barrier skews the cutaneous cytokine milieu toward a Th2 pattern. 26 -29,77-79 However, since Th2 inflammation itself down-regulates FLG expression, 25 as well as expression of several other epidermal proteins of importance for the barrier, 23 it remains unknown how FLG mutations alter skin barrier function. To determine the impact and mechanisms whereby FLG deficiency compromises permeability barrier structure and function, we studied here a cohort of IV patients largely devoid of clinical signs of cutaneous inflammation.…”

“…It is difficult to assess how FLG deficiency leads to the barrier abnormality in AD, because Th2-dominant inflammation can secondarily com-promise barrier function by multiple mechanisms, 23 including an acquired reduction in FLG. 24,25 Thus, whether FLG deficiency suffices to provoke a barrier abnormality, and how such an abnormality might occur, remain unknown. The possibility that FLG deficiency suffices to provoke a barrier abnormality is supported by recent studies in flaky tail (ft/ft) mice, which demonstrate abnormalities in barrier function in association with an absence of FLG.…”

Cutaneous exposure to clinically-relevant pigeon pea (Cajanus cajan) proteins promote TH2-dependent sensitization and IgE-mediated anaphylaxis in Balb/c mice

“…Impairment in filaggrin (due to gene defect) is commonly associated with various allergic diseases like AD, FA, AR as well as allergic asthma (Valdman-Grinshpoun et al 2012;Ziyab et al 2014). Certain T H 2 cytokines like IL-4 and IL-13 may modulate filaggrin expression; thus, changes in their expression may ultimately lead to skin barrier dysfunction (Howell et al 2009). In concordance with the findings concerning the cytokines here, decreased levels of filaggrin were found exclusively in the skin protein of EC-sensitized mice.…”