Tools
ToolsLeitch, Claire S., Natafji, Eenass, Yu, Cunjing, Abdul-Ghaffar, Sharizan, Madarasingha, Nayani, Venables, Zoë C., Chu, Roland, Fitch, Paul M., Muinonen-Martin, Andrew J., Campbell, Linda E., McLean, W. H. Irwin, Schwarze, Jürgen, Howie, Sarah E. M. and Weller, Richard B. (2016) Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells. Journal of Allergy and Clinical Immunology, 138 (2). 482-490.e7. ISSN 0091-6749
Preview |
PDF (Leitch_etal_2016_JACI)
- Published Version
Available under License Creative Commons Attribution. Download (2MB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | atopic dermatitis,costimulatory molecules,filaggrin,langerhans cells,urocanic acid,immunology and allergy,immunology ,/dk/atira/pure/subjectarea/asjc/2700/2723 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 19 Mar 2025 14:30 |
| Last Modified: | 28 Mar 2025 13:15 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/98811 |
| DOI: | 10.1016/j.jaci.2015.11.040 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |