Elisabeth Geiger

IL-4 induces the intracellular expression of the α 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. OBJECTIVES 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. CONCLUSION 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.

Characterization of monocyte subtypes in the allergic form of atopic eczema/dermatitis syndrome

Background:  Monocyte (Mo) subsets exhibiting distinct phenotypic and functional properties identified in peripheral blood are assumed to be under the control of soluble factors from their surrounding micromilieu. Atopic eczema/dermatitis syndrome (AEDS) is accompanied by humoral and cellular alterations among which an increased expression of the high‐affinity receptor for IgE (FcεRI) on antigen presenting cells, like Mo, could be found. Therefore we analyzed the assembly of circulating Mo populations and their FcεRI surface expression during the course of AEDS.

Limited reliability of E-cadherin as a specific marker for in vitro-generated Langerhans cells.

Langerhans cells (LC) are a unique population of dendritic cells (DC) found in the epidermis where they can be identified by the expression of CD1a, E-cadherin and cytoplasmic Birbeck granules (BG) as their hallmark. Over the past years many techniques have been described to generate LC in vitro from either monocytes or CD34+ hematopoietic cell progenitors. Antibodies against Lag and Langerin (two epitopes associated with BG) and E-cadherin (a Ca2+-dependent homophilic adhesion molecule) have been used to detect in vitro-generated LC. In this study we investigated whether the expression of E-cadherin on in vitro-generated CD1a+ from either CD34+ cells or monocytes is able to discriminate LC from other DC. Our results demonstrate that E-cadherin alone is not a reliable marker to specifically identify in vitro-generated LC.

EcɛRI Expressing Dendritic Cells: The Missing Link in the Pathophysiology of Atopic Dermatitis ?

Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disease clinically and histologically highly similar to allergic contact dermatitis. Recently, it has been proposed to subdivide AD into 2 distinct forms: the extrinsic form (occuring in the context of sensitization toward environmental allergens) and the intrinsic form (occuring in the absence of any typical atopicalbackground) (1). While the pathophysiology of the intrinsic form remains almost elusive, tremendous progress has been made in the understanding of the extrinsic form. Thus, since IgE plays a major role in other atopic diseases, such as asthma and rhinitis, it is assumed that, in this extrinsic form, IgE also mediates the specificity of the inflammatory conditions in the skin.