Epidermal filaggrin deficiency mediates increased systemic T-helper 17 immune response.
Br J Dermatol
; 175(4): 706-12, 2016 Oct.
Article
in En
| MEDLINE
| ID: mdl-26997324
ABSTRACT
BACKGROUND:
Cellular T-helper (Th)17 infiltrates dominate skin inflammation in filaggrin-deficient flaky tail (ft/ft) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss-of-function mutations in the filaggrin gene (FLG) for increased peripheral Th17 cells is unclear.OBJECTIVES:
To study whether mutations in FLG influence the frequency of peripheral Th17 cells.METHODS:
We studied blood samples from six adults with mutations in FLG and five controls without mutations for frequencies of cytokine-producing CD4(+) T cells. We evaluated ft/ft mice and wild-type (WT) control mice for interleukin (IL)-17-producing CD4(+) T cells in naive mice and following 2,4-dinitrofluorobenzene (DNFB) challenge. In addition, the T-cell receptor (TCR) Vß-chain repertoire was analysed by flow cytometry.RESULTS:
Human studies showed increased frequency of peripheral Th17 cells in FLG mutation carriers when compared with WT individuals. Mouse studies showed increased frequency of peripheral Th17 cells in adult ft/ft mice but not in 2-week-old ft/ft mice. Moreover, altered TCR Vß-chain repertoire was found in ft/ft mice when compared with WT mice. An increased frequency of CD4(+) Vß10(+) T cells producing IL-17 was found in the spleen of adult ft/ft mice when compared with WT mice. Finally, DNFB challenge induced an increased number of Th17 cells in ft/ft mice compared with WT mice.CONCLUSIONS:
Deficiency of filaggrin appeared to be a driver of increased peripheral levels of Th17 cells. This increase must be acquired as peripheral Th17 cells were found in adult ft/ft mice but not in 2-week-old ft/ft mice indicating involvement of exogenous factors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Th17 Cells
/
Immunity, Cellular
/
Intermediate Filament Proteins
/
Mutation
Limits:
Adult
/
Animals
/
Humans
Language:
En
Journal:
Br J Dermatol
Year:
2016
Document type:
Article
Affiliation country:
Denmark