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Filaggrin-null Mutations Are Associated With Increased Maturation Markers On Langerhans Cells.

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Filaggrin-null Mutations Are Associated With Increased Maturation Markers On Langerhans Cells.

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Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells.

Claire S Leitch¹, Eenass Natafji², Cunjing Yu²

¹Department of Dermatology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom; MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.

The Journal of Allergy and Clinical Immunology

|March 4, 2016

View abstract on PubMed

Summary

This summary is machine-generated.

Filaggrin (FLG) mutations increase Langerhans cell maturation in skin, regardless of atopic dermatitis (AD). Cis-urocanic acid (UCA) reduces dendritic cell maturation, suggesting a link between FLG deficiency and immune dysregulation.

Keywords:

Filaggrin Langerhans cells atopic dermatitis costimulatory molecules urocanic acid

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Area of Science:

Immunodermatology
Molecular Biology
Cellular Immunology

Background:

Filaggrin (FLG) mutations are a primary risk factor for atopic dermatitis (AD), affecting 50% of severe AD patients.
FLG-null alleles are found in 7-10% of the general population, highlighting a significant genetic predisposition.

Purpose of the Study:

To investigate the link between FLG-null mutations and epidermal antigen-presenting cell (APC) maturation in AD.
To determine the immunomodulatory effects of cis-urocanic acid (UCA), an FLG breakdown product, on dendritic cells.

Main Methods:

Epidermal APCs from nonlesional skin of subjects with and without AD were analyzed using flow cytometry and confocal microscopy.
Monocyte-derived dendritic cells from healthy volunteers were treated with cis- and trans-UCA to assess phenotypic changes via flow cytometry.

Main Results:

FLG-null subjects exhibited increased CD11c expression on epidermal APCs and a higher number of CD83+ Langerhans cells.
In vitro, cis-UCA significantly reduced costimulatory molecule expression on dendritic cells and enhanced their ability to induce regulatory T cells.

Conclusions:

FLG-null mutations are associated with more mature Langerhans cells in nonlesional skin, independent of AD status.
Cis-UCA demonstrates immunomodulatory effects, reducing dendritic cell maturation and promoting regulatory T cell induction, suggesting a novel mechanism in FLG deficiency-related immune dysregulation.