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http://purl.uniprot.org/citations/26934939http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26934939http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2015.11.040"xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Yu C."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"McLean W.H."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Chu R."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Howie S.E."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Campbell L.E."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Schwarze J."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Fitch P.M."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Muinonen-Martin A.J."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Abdul-Ghaffar S."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Leitch C.S."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Madarasingha N."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Natafji E."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Venables Z.C."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/author"Weller R.B."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/name"J Allergy Clin Immunol"xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/pages"482-490.e7"xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/title"Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells."xsd:string
http://purl.uniprot.org/citations/26934939http://purl.uniprot.org/core/volume"138"xsd:string
http://purl.uniprot.org/citations/26934939http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26934939
http://purl.uniprot.org/citations/26934939http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26934939
http://purl.uniprot.org/uniprot/#_I0B0K3-mappedCitation-26934939http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26934939