414 Influence of filaggrin genotype on regulatory T cells in atopic dermatitis

Abstract

Atopic dermatitis (AD) is considered to result from skin barrier impairment coupled with environmental factors and abnormal immune reactivity. Although previous studies describe an important role of regulatory T cells (Tregs) in the pathogenesis of AD, the interaction between Tregs and epidermal barrier dysfunction in AD patients remains unclear. We here report a heterogeneous AD cohort, which has been characterized for filaggrin (FLG) mutation status by next generation sequencing and for phenotypical grading by assessment of EASI score, grade of erythema, transepidermal water loss (TEWL) and total serum IgE. AD patients revealed an increased EASI score, grade of erythema and TEWL, regardless of filaggrin genotype, when compared to healthy controls. Total serum IgE was increased in AD patients without filaggrin mutations when compared to healthy controls and AD patients carrying filaggrin null mutations. For characterization of circulating Tregs we identified demethylation of CpG dinucleotides in a conserved region of FoxP3 intron 1, representing stable Tregs with suppressive function, and percentages of CD4+ CD25+ CD127-/low Tregs in peripheral blood of AD patients and healthy controls. Although our cohort presented no significant differences in percentages of Tregs with demethylated FoxP3i1, we observed an increased proportion of CD4+ CD25+ CD127-/low Tregs within the CD4+ cell population only in FLG wt/wt AD patients. Within the Treg population, proportions of effector CCR4+CD45RAlow Tregs were enhanced, exhibiting increased proportions of Th2 Tregs, whereas proportions of Th1 Tregs were decreased in FLG wt/wt AD patients. Thus, in AD patients neither disease severity nor filaggrin genotype influences levels of suppressive Tregs, while Tregs with plasticity are increased in AD patients without filaggrin mutations.