Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells.
J Allergy Clin Immunol
; 138(2): 482-490.e7, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-26934939
ABSTRACT
BACKGROUND:
Mutations in the gene encoding filaggrin (FLG), an epidermal structural protein, are the strongest risk factor identified for the development of atopic dermatitis (AD). Up to 50% of patients with moderate-to-severe AD in European populations have FLG-null alleles compared with a general population frequency of 7% to 10%.OBJECTIVE:
This study aimed to investigate the relationship between FLG-null mutations and epidermal antigen-presenting cell (APC) maturation in subjects with and without AD. Additionally, we investigated whether the cis isomer of urocanic acid (UCA), a filaggrin breakdown product, exerts immunomodulatory effects on dendritic cells.METHODS:
Epidermal APCs from nonlesional skin were assessed by using flow cytometry (n = 27) and confocal microscopy (n = 16). Monocyte-derived dendritic cells from healthy volunteers were used to assess the effects of cis- and trans-UCA on dendritic cell phenotype by using flow cytometry (n = 11).RESULTS:
Epidermal APCs from FLG-null subjects had increased CD11c expression. Confocal microscopy confirmed this and additionally revealed an increased number of epidermal CD83(+) Langerhans cells in FLG-null subjects. In vitro differentiation in the presence of cis-UCA significantly reduced costimulatory molecule expression on monocyte-derived dendritic cells from healthy volunteers and increased their ability to induce a regulatory T-cell phenotype in mixed lymphocyte reactions.CONCLUSIONS:
We show that subjects with FLG-null mutations have more mature Langerhans cells in nonlesional skin irrespective of whether they have AD. We also demonstrate that cis-UCA reduces maturation of dendritic cells and increases their capacity to induce regulatory T cells, suggesting a novel link between filaggrin deficiency and immune dysregulation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Células de Langerhans
/
Proteínas de Filamentos Intermediários
/
Mutação
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article