IL-4 induces the intracellular expression of the alpha chain of the high-affinity receptor for IgE in in vitro-generated dendritic cells.
BACKGROUND
Recent findings have shown that the surface expression of the high-affinity receptor for IgE (FcepsilonRI) on human CD1a(+) Langerhans cells (LC) and related dendritic cells (DC) in the skin, despite a constant intracellular expression of its alpha chain (FcepsilonRIalpha), is highly up-regulated in atopic dermatitis. Moreover, this surface expression correlates with the IgE serum level, strongly suggesting yet-to-be-defined common signals in the regulation of FcepsilonRI display on LC/DC and IgE synthesis.


OBJECTIVE
In this study we examined the influence of different cytokines on the expression of FcepsilonRI on in vitro-generated CD1a(+) LC/DC.


METHODS
CD34(+) precursor cells were isolated from cord blood with use of high-gradient magnetic cell sorting, cultured with GM-CSF, TNF-alpha, IL-4, or IFN-gamma, and surface and cytoplasmic staining for flow cytometry were performed.


RESULTS
IL-4 strongly enhanced the generation of CD1a(+) LC/DC and also up-regulated the expression of the skin-homing structures E-cadherin and cutaneous lymphocyte antigen. In contrast, IFN-gamma was found to suppress the E-cadherin expression and to be a strong antagonist of IL-4 by inhibiting the production of CD1a(+) cells. Most important, IL-4 induced the cytoplasmic expression of FcepsilonRIalpha in CD1a(+) LC/DC but not its surface expression. This up-regulation was antagonized by IFN-gamma.


CONCLUSIONS
IL-4 is not only a key cytokine in the regulation of IgE but also induces the expression of its receptor binding chain as well as up-regulation of skin homing molecules on LC/DC. Expression of these structures during generation of LC/DC reflects the in vivo situation encountered in LC.
Geiger
E
E
Department of Dermatology, Friedrich-Wilhelms-University, Bonn, Germany.
Magerstaedt
R
R
Wessendorf
J H
JH
Kraft
S
S
Hanau
D
D
Bieber
T
T
D018949:Antigens, CD1 / Q000032:analysis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007139:Immunoglobulin epsilon-Chains / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*
D018949:Antigens, CD1; D007139:Immunoglobulin epsilon-Chains; D020033:Protein Isoforms; D012333:RNA, Messenger; D011961:Receptors, Fc; D017455:Receptors, IgE; D015847:Interleukin-4; D007371:Interferon-gamma