An Essential Role for CD44 Variant Isoforms in Epidermal Langerhans Cell and Blood Dendritic Cell Function

doi:10.1083/jcb.137.5.1137

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© The Rockefeller University Press, 0021-9525/1997//1137 $5.00
The Journal of Cell Biology, Volume 137, Number 5, , 1997 1137-1147

Article

An Essential Role for CD44 Variant Isoforms in Epidermal Langerhans Cell and Blood Dendritic Cell Function

Johannes M. Weiss^*, Jonathan Sleeman, Andreas C. Renkl^*, Henning Dittmar^*, Christian C. Termeer^*, Sabine Taxis^*, Norma Howells, Martin Hofmann, Gabriele Köhler, Erwin Schöpf^*, Helmut Ponta, Peter Herrlich, and Jan C. Simon^*

^* Department of Dermatology, Department of Pathology, Freiburg University, D-79104 Freiburg, Germany; and Institute of Genetics, Forschungszentrum Karlsruhe, Germany

Upon antigen contact, epidermal Langerhans cells (LC) and dendriticcells (DC) leave peripheral organs and home to lymph nodes viathe afferent lymphatic vessels and then assemble in the paracortical T cell zone and present antigen to T lymphocytes. Since splicevariants of CD44 promote metastasis of certain tumors to lymphnodes, we explored the expression of CD44 proteins on migratingLC and DC. We show that upon antigen contact, LC and DC upregulatepan CD44 epitopes and epitopes encoded by variant exons v4,v5, v6, and v9. Antibodies against CD44 epitopes inhibit theemigration of LC from the epidermis, prevent binding of activatedLC and DC to the T cell zones of lymph nodes, and severelyinhibit their capacity to induce a delayed type hypersensitivityreaction to a skin hapten in vivo. Our results demonstratethat CD44 splice variant expression is obligatory for the migration and function of LC and DC.

Abbreviations used in this paper: ANOVA, analysis of variance; CD44v, CD44 variant; DC, dendritic cells; DTH, delayed type hypersensitivity; ECM, extracellular matrix; GM-CSF, granulocyte macrophage colony stimulating factor; HA, hyaluronate; LC, Langerhans cells; LN, lymph nodes; MFI, mean fluorescence intensity.

Address all correspondence to Johannes M. Weiss, Departmentof Dermatology, University of Freiburg, Hauptstrasse 7, D-79104Freiburg, Germany. Tel.: 49 761-270-6831. Fax: 49 761-270-6829.

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Banerji, S., Ni, J., Wang, S.-X., Clasper, S., Su, J., Tammi, R., Jones, M., Jackson, D. G. (1999). LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan. JCB 144: 789-801 [Abstract] [Full Text]
Wielenga, V. J. M., Smits, R., Korinek, V., Smit, L., Kielman, M., Fodde, R., Clevers, H., Pals, S. T. (1999). Expression of CD44 in Apc and Tcf Mutant Mice Implies Regulation by the WNT Pathway. Am. J. Pathol. 154: 515-523 [Abstract] [Full Text]
Wang, B., Zhuang, L., Fujisawa, H., Shinder, G. A., Feliciani, C., Shivji, G. M., Suzuki, H., Amerio, P., Toto, P., Sauder, D. N. (1999). Enhanced Epidermal Langerhans Cell Migration in IL-10 Knockout Mice. J. Immunol. 162: 277-283 [Abstract] [Full Text]
Haegel-Kronenberger, H., de la Salle, H., Bohbot, A., Oberling, F., Cazenave, J.-P., Hanau, D. (1998). Adhesive and/or Signaling Functions of CD44 Isoforms in Human Dendritic Cells. J. Immunol. 161: 3902-3911 [Abstract] [Full Text]
Kocikova, A., Kolesaric, A., Koszik, F., Stingl, G., Elbe-Burger, A. (1998). Murine Langerhans Cells Cultured Under Serum-Free Conditions Mature into Potent Stimulators of Primary Immune Responses In Vitro and In Vivo. J. Immunol. 161: 4033-4041 [Abstract] [Full Text]
Reinisch, W, Heider, K-H, Oberhuber, G, Dejaco, C, Mullner, M, Adolf, G R, Gasche, C (1998). Poor diagnostic value of colonic CD44v6 expression and serum concentrations of its soluble form in the differentiation of ulcerative colitis from Crohn's disease. Gut 43: 375-382 [Abstract] [Full Text]
Randolph, G. J., Beaulieu, S., Pope, M., Sugawara, I., Hoffman, L., Steinman, R. M., Muller, W. A. (1998). A physiologic function for p-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels. Proc. Natl. Acad. Sci. USA 95: 6924-6929 [Abstract] [Full Text]
Sherman, L., Wainwright, D., Ponta, H., Herrlich, P. (1998). A splice variant of CD44 expressed in the apical ectodermal ridge presents fibroblast growth factors to limb mesenchyme and is required for limb�outgrowth. Genes Dev. 12: 1058-1071 [Abstract] [Full Text]
Sauter, B., Foedinger, D., Sterniczky, B., Wolff, K., Rappersberger, K. (1998). Immunoelectron Microscopic Characterization of Human Dermal Lymphatic Microvascular Endothelial Cells: Differential Expression of CD31, CD34, and Type IV Collagen with Lymphatic Endothelial Cells vs Blood Capillary Endothelial Cells in Normal Human Skin, Lymphangioma, and Hemangioma In Situ. J. Histochem. Cytochem. 46: 165-176 [Abstract] [Full Text]
Matter, N., Marx, M., Weg-Remers, S., Ponta, H., Herrlich, P., Konig, H. (2000). Heterogeneous Ribonucleoprotein A1 Is Part of an Exon-specific Splice-silencing Complex Controlled by Oncogenic Signaling Pathways. J. Biol. Chem. 275: 35353-35360 [Abstract] [Full Text]
Shikano, S., Bonkobara, M., Zukas, P. K., Ariizumi, K. (2001). Molecular Cloning of a Dendritic Cell-associated Transmembrane Protein, DC-HIL, That Promotes RGD-dependent Adhesion of Endothelial Cells through Recognition of Heparan Sulfate Proteoglycans. J. Biol. Chem. 276: 8125-8134 [Abstract] [Full Text]
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Ariizumi, K., Shen, G.-L., Shikano, S., Xu, S., Ritter, R. III, Kumamoto, T., Edelbaum, D., Morita, A., Bergstresser, P. R., Takashima, A. (2000). Identification of a Novel, Dendritic Cell-associated Molecule, Dectin-1, by Subtractive cDNA Cloning. J. Biol. Chem. 275: 20157-20167 [Abstract] [Full Text]