Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum.
The presence of loss-of-function mutations in the filaggrin gene (FLG) is the main predisposing factor for AD FLG mutations show ethnic and geographical variations, even between European populations.
Then, we assessed the proliferation and the production of the Th22 chemokines CCR4 and CCR10 by ICOSL-stimulated AD peripheral blood mononuclear cells (PBMCs) as well as their effects on keratinocyte filaggrin production.
Filaggrin (FLG) loss of function variants have been associated with the onset and severity of atopic dermatitis and are the most common genetic association with AD.
The discovery of the filaggrin gene was important in the emerging model for AD pathogenesis, combining skin barrier function with adaptive and innate immunity.
The contribution of filaggrin gene mutations to atopic dermatitis has increased our appreciation of the role barrier perturbations play in inflammatory dermatoses.
FLG loss-of-function mutations were significantly associated with AD onset in infancy (≤2 years) (P < 0.001, OR 3.54, 95% CI 1.88-6.65), but not with AD onset in childhood (≥3 years) (P = 0.981, OR 0.99, 95% CI 0.29-3.36), and none of the children in the present cohort who developed AD at 5 years of age or later carried FLG loss-of-function mutations.
Recent studies have identified a crucial role for the aryl hydrocarbon receptor (AHR) in controlling the gene expression of filaggrin and other skin barrier proteins, suggesting an underlying association between AHR and AD pathogenesis.
Children with early, late transient and persistent eczema more often had a filaggrin mutation or additional risk alleles (range OR: 1.07, 95%CI 1.02-1.12 and OR 2.21, 95%CI 1.39-3.50).
Major limitations of published studies were low numbers of individuals with AD and FLG loss-of-function mutations and exposure to specific environmental factors (n=5 to 94), and variation in exposure definitions.
Overall, these results show that Tregs may participate into AD pathogenesis and that FLG null mutations exert further modifications on specific subpopulations of circulating Tregs.
Multiple factors are associated with colonization of AD skin by <i>S. aureus</i>, including the strength of <i>S. aureus</i>-corneocyte adhesion, deficiency of antimicrobial peptides, decreased levels of filaggrin and filaggrin degradation products, overexpressed Th2/Th17 cytokines, microbial dysbiosis and altered lipid profiles.<i>S. aureus</i> colonization on AD skin causes skin barrier dysfunction through virulence factors such as superantigens (toxins), enzymes and other proteins.
OR10G7 expression was significantly increased in skin biopsy specimens from patients with AD compared with those from HC subjects (P = .01) and inversely correlated with FLG-1 expression (P = .009).
Recent investigations implicate disease severity and persistence, age of onset, parental atopic history, filaggrin (FLG) mutations, polysensitization, and the nonrural environment among risk factors for development of multiple atopic comorbidities in young children with AD.
Studies have shown that AD harbors different endotypes across different age groups and ethnicities and according to IgE levels and filaggrin mutation status.
Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD <i>FA</i>+ were substantially lower than in AD <i>FA</i>- and NA skin.
These results suggest that β-carotene reduces skin inflammation through the suppressed expression of inflammatory factors or the activity of MMPs as well as the promotion of filaggrin expression in AD-like skin.