Characterization of FcepsilonRI-bearing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic cells in atopic dermatitis.
BACKGROUND
The high-affinity receptor for IgE (FcepsilonRI) on myeloid dendritic cells has been shown to play a major role in atopic dermatitis (AD). Plasmacytoid dendritic cells (pDCs), which are instrumental in the defense of viral infections, are present in reduced amounts in the skin of patients with AD, which is characterized by a high susceptibility to viral infections.


OBJECTIVE
We explored phenotypical and functional characteristics of pDC in the peripheral blood of patients with AD and healthy individuals.


METHODS
Blood dendritic cell antigen-2+CD123+ pDCs were enriched from the peripheral blood of patients with AD and studied in functional assays.


RESULTS
Skin-homing molecules such as cutaneous lymphocyte antigen and L-selectin CD62L were expressed in lower levels on pDCs of patients with AD. pDCs expressed high amounts of IgE-occupied FcepsilonRI. Further, FcepsilonRI aggregation on pDCs impaired the surface expression of MHC I and II, induced the production of IL-10, and enhanced the apoptosis of pDCs. Importantly, FcepsilonRI preactivated pDC produced less IFN-alpha and IFN-beta after stimulation with CpG motifs and enhanced the outcome of immune responses of the TH2 type.


CONCLUSIONS
From these data, we conclude that FcepsilonRI-bearing pDCs from patients with AD (1) are different from pDCs of healthy individuals, (2) might be important in the pathophysiology of AD, and (3) contribute to the enhanced susceptibility of patients with AD to viral infections.
Department of Dermatology, University of Bonn, Germany. Natalija.Novak@ukb.uni-bonn.de
Natalija
N
Novak
Jean-Pierre
JP
Allam
Tobias
T
Hagemann
Claudia
C
Jenneck
Sylvia
S
Laffer
Rudolf
R
Valenta
Jarema
J
Kochan
Thomas
T
Bieber
D000328:Adult; D000368:Aged; D017209:Apoptosis; D019013:CD40 Antigens / Q000032:analysis; D016764:Cell Polarity; D003713:Dendritic Cells / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D053650:Interleukin-3 Receptor alpha Subunit; D037181:Lectins, C-Type / Q000032:analysis*; D008562:Membrane Glycoproteins; D008875:Middle Aged; D017455:Receptors, IgE / Q000032:analysis*; D011971:Receptors, Immunologic; D016185:Receptors, Interleukin-3 / Q000032:analysis*
D019013:CD40 Antigens; C443299:CLEC4C protein, human; C115022:IL3RA protein, human; D016898:Interferon-alpha; D053650:Interleukin-3 Receptor alpha Subunit; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D016185:Receptors, Interleukin-3; D016753:Interleukin-10; D016899:Interferon-beta