Aberrant function of peripheral blood myeloid and plasmacytoid dendritic cells in atopic dermatitis patients.
BACKGROUND
Dendritic cells (DCs) can act both as innate cells in host defense and as antigen-presenting cells for naive T cells in adaptive immunity. These functions, among others, are determined by the level of production of particular cytokines. Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by an initial phase predominated by T(H)2 cytokines that switches into a second, more chronic T(H)1-dominated eczematous phase.


OBJECTIVE
To assess to what extent the AD phenotype is associated with an aberrant phenotype and function of DCs.


METHODS
Classic CD1c(+)/blood DC antigen (BDCA)-1(+) myeloid (m) DCs and CD304(+)/BDCA4(+) plasmacytoid (p) DCs, the natural IFN-producing cells, were isolated from peripheral blood of patients with AD and healthy controls and analyzed for their phenotype and function.


RESULTS
Purified CD1c(+)/BDCA1(+) mDCs from patients with AD showed a selective and dramatic reduction of IL-12p70 and TNF-alpha release. IL-12p70 reduction was attributed to a defective expression of both IL-12p35 and IL-12p40 subunits. Accordingly, mature CD1c(+)/BDCA1(+) mDCs from patients with AD induced considerably less IFN-gamma-producing and more IL-4-producing T(H) cells compared with mDCs from healthy controls. In addition, CD304(+)/BDCA4(+) pDCs from patients with AD produced significantly lower levels of IFN-alpha compared with healthy controls.


CONCLUSIONS
Myeloid DCs and pDCs from patients with AD show defective IL-12, TNF-alpha, and IFN-alpha production, which may contribute to increased susceptibility to infection and to the maintenance of the T(H)2 cell-mediated allergic state in patients with AD.
Department of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
M Cristina
MC
Lebre
Toni M M
TM
van Capel
Jan D
JD
Bos
Edward F
EF
Knol
Martien L
ML
Kapsenberg
Esther C
EC
de Jong
D000328:Adult; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D010641:Phenotype; D055815:Young Adult
D018949:Antigens, CD1; D000954:Antigens, Surface; C437944:CD1C protein, human; D016207:Cytokines; D006023:Glycoproteins