Induction of FcεRIα mRNA and Protein Synthesis by Interleukin 4 in CD34+ Cells-Derived Cd1a+ Dendritic Cells
IgE-bearing human epidermal Langerhans cells (LC) are suspected of playing a key role in the pathogenesis of atopic dermatitis (AD). We and others have shown that these cells bind IgE via the high affinity receptor Fc epsilon RI (FcεRI) (1, 2). Recent findings have shown that the expression of this receptor on LC and related dendritic cells in the skin is highly upregulated in lesions skin of AD when compared with nonatopic individuals and this is correlated to a high IgE serum levels (3). Functionally, LC from normal skin differ from those of atopic skin in terms of calcium mobilization upon receptor ligation (4). Beside qualitative alterations in the activation cascade, unresponsiveness also may be related to inefficient triggering in normal LC displaying low amounts of receptors. Thus, the variations in receptor expression may be crucial for the outcome of the signal transduction initiated by FcεRI-cross-linking on LC, implying the need of a better understanding of the mechanisms regulating the receptor display on LC. However, detailed functional, biochemical and molecular biological analysis of FcεRI + LC is hampered by the limited number of LC routinely obtained from skin biopsies or surgical samples. Recently several cytokines, especially granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-α), have been identified that speed the development of dendritic cells from blood and bone marrow precursors in suspension cultures (5, 6, 7, 8, 9). We took advantage of this progress to establish a model for the study of the regulation of FcεRI on LC and other dendritic cells.
KeywordsDendritic Cell Atopic Dermatitis Calcium Mobilization Peripheral Blood Progenitor Cell Bone Marrow Precursor
Unable to display preview. Download preview PDF.
- 1.Bieber, T., de la Salle, H., Wollenberg, A., Hakimi, J., Chizzonite, R., Ring, J., Hanau, D., and de la Salle, C., Human Epidermal Langerhans cells Express the High affinity Receptor for Immunoglobulin F (FcsRI), J. Exp. Med. 175: 1285 (1992)Google Scholar
- 2.Wang, B., Ricger, A. Kilgus, O. Ochiai, K., Maurer, D., Fodinge, D. K.net, J.P. and Stingl, G., Epidermal Langerhans cells from normal human skin bind monomeric IgE via FccRI. J. Exp. Med. 175: 1285 (1992)Google Scholar
- 6.Szabolcs, R, Feller, E.D., Moore, Mas and Youg, J.W., Progenitor recruitment and in vitro expansion of immunostimmulatory dendrtic cells from human CD34’ bone marrow cells by c-kit-ligand, GM-CSF and TNF-alpha. Adv Exp Med Biol 378. 17: 17Google Scholar
- 8.Mackensen, A., Herbst, B., Kohler, G., Wolffvorbeck, G., Rosenthal, F.M., Veelken, H., Kulmburg, P., Schaefer, H.E., Mertelsmann, R. and Lindemann, A., Delineation of the dendritic cell lineage by generating large numbers of Birbeck granule-positive Langerhans cells from human peripheral blood progenitor cells in vitro. Blood. 86: 2699 (1995)PubMedGoogle Scholar
- 9.Reid, C. D., Stackpoole, A., Meager, A. and Tikerpae, J., Progenitor recruitment and in vitro expansion of immunostimulatory dendritic cells from human CD34* bone marrow cells by c-kit-ligand, GM-CSF, and TNF alpha Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34’ progenitors in human bone marrow. J. Immunol. 142, 2681 (1992)Google Scholar
- 11.Zhou, L.-J.and Tedder, T.F. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J.lmmunol. 154, 3821 (1995)Google Scholar
- 12.Moisialos, G., Birkenbach, M., Ayehunie, S., Matasumura, F., Pinkus, G.S., Kieff, E. and Langhoff, E. Circulating human dendritic cells differentially express high levels of a 55-KD actin bundling protein. Am. J. Paththol. 148. 593 (1996)Google Scholar
- 13.Toru, H., C. Ra, S. Nonoyama, K., Suzuki, J. Yata and T. Nakahata Induction of the high-affinity IgE receptor (Fe epsilon RI) on human mast cells by IL-4. Int.lmmunol 8: 1367–1373 (1996)Google Scholar