Filaggrin null mutations associate with increased frequencies of allergen-specific CD4+ T-helper 2 cells in patients with atopic eczema.
BACKGROUND
Filaggrin null mutations associate with atopic eczema and also with asthma when present with eczema. However, while epidermal dysfunction is an important factor in disease pathogenesis, it is unclear how such dysfunction interacts with immune responses to contribute to cutaneous and other inflammatory atopic disease.


OBJECTIVE
To gain a better understanding of the mechanisms underlying such predisposition in order to understand different disease phenotypes and possibly identify potential treatment targets.


METHODS
We studied 33 individuals with atopic eczema and used interleukin-4 immunospot and human leucocyte antigen class II tetrameric complexes to investigate the peripheral blood allergen-specific CD4+ T-cell responses.


RESULTS
Filaggrin null mutations associated with significantly (P<0·05) higher frequencies of allergen-specific CD4+ T-helper 2 cell responses.


CONCLUSIONS
These data would support a model where barrier dysfunction possibly promotes greater allergen penetration and delivery to drive allergen-specific CD4+ T cells. This could further contribute to respiratory and cutaneous inflammatory disease.
McPherson
T
T
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Biomedical Research Centre, OX3 9DS, U.K. tess.mcpherson@imm.ox.ac.uk
Sherman
V J
VJ
Aslam
A
A
Crack
L
L
Chan
H
H
Lloyd-Lavery
A
A
Jones
L
L
Ardern-Jones
M
M
Ogg
G
G
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D004485:Eczema / Q000235:genetics* / Q000276:immunology*; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular; D015847:Interleukin-4 / Q000276:immunology; D007381:Intermediate Filament Proteins / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006680:HLA Antigens; D007381:Intermediate Filament Proteins; D015847:Interleukin-4