Abstract
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.
Similar content being viewed by others
References
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252
Bieber T, Rieger A, Neuchrist C, Prinz JC, Rieber EP, Boltz-Nitulescu G, Scheiner O, Kraft D, Ring J, Stingl G (1989) Induction of Fc epsilon R2/CD23 on human epidermal Langerhans cells by human recombinant interleukin 4 and gamma interferon. J Exp Med 170:309–314
Blauvelt A, Katz SI, Udey MC (1995) Human Langerhans cells express E-cadherin. J Invest Dermatol 104:293–296
Borkowski TA, Van Dyke BJ, Schwarzenberger K, McFarland VW, Farr AG, Udey MC (1994) Expression of E-cadherin by murine dendritic cells: E-cadherin as a dendritic cell differentiation antigen characteristic of epidermal Langerhans cells and related cells. Eur J Immunol 24:2767–2774
Borkowski TA, Letterio JJ, Farr AG, Udey MC (1996) A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: the skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells. J Exp Med 184:2417–2422
Borkowski TA, Letterio JJ, Mackall CL, Saitoh A, Wang XJ, Roop DR, Gress RE, Udey MC (1997) A role for TGFbeta1 in langerhans cell biology. Further characterization of the epidermal Langerhans cell defect in TGFbeta1 null mice. J Clin Invest 100:575–581
Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360:258–261
Cumberbatch M, Dearman RJ, Kimber I (1996) Adhesion molecule expression by epidermal Langerhans cells and lymph node dendritic cells: a comparison. Arch Dermatol Res 288:739–744
Ebner S, Lenz A, Reider D, Fritsch P, Schuler G, Romani N (1998) Expression of maturation-/migration-related molecules on human dendritic cells from blood and skin. Immunobiology 198:568–587
Esch TR, Jonsson MV, Levanos VA, Poveromo JD, Sorkin BC (2000) Leukocytes infiltrating the submandibular glands of NOD mice express E-cadherin. J Autoimmun 15:387–393
Geiger E, Magerstaedt R, Wessendorf JH, Kraft S, Hanau D, Bieber T (2000) IL-4 induces the intracellular expression of the alpha chain of the high-affinity receptor for IgE in in vitro-generated dendritic cells. J Allergy Clin Immunol 105:150–156
Geissmann F, Prost C, Monnet JP, Dy M, Brousse N, Hermine O (1998) Transforming growth factor beta1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J Exp Med 187:961–966
Geissmann F, Revy P, Regnault A, Lepelletier Y, Dy M, Brousse N, Amigorena S, Hermine O, Durandy A (1999) TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells. J Immunol 162:4567–4575
Guironnet G, Dezutter-Dambuyant C, Vincent C, Bechetoille N, Schmitt D, Peguet-Navarro J (2002) Antagonistic effects of IL-4 and TGF-beta1 on Langerhans cell-related antigen expression by human monocytes. J Leukoc Biol 71:845–853
Hanau D, Fabre M, Schmitt DA, Stampf JL, Garaud JC, Bieber T, Grosshans E, Benezra C, Cazenave JP (1987) Human epidermal Langerhans cells internalize by receptor-mediated endocytosis T6 (CD1 "NA1/34") surface antigen. Birbeck granules are involved in the intracellular traffic of the T6 antigen. J Invest Dermatol 89:172–177
Jakob T, Ring J, Udey MC (2001) Multistep navigation of Langerhans/dendritic cells in and out of the skin. J Allergy Clin Immunol 108:688–696
Kashihara M, Ueda M, Horiguchi Y, Furukawa F, Hanaoka M, Imamura S (1986) A monoclonal antibody specifically reactive to human Langerhans cells. J Invest Dermatol 87:602–607
Kawamura T, Qualbani M, Thomas EK, Orenstein JM, Blauvelt A (2001) Low levels of productive HIV infection in Langerhans cell-like dendritic cells differentiated in the presence of TGF-beta1 and increased viral replication with CD40 ligand-induced maturation. Eur J Immunol 31:360–368
Kraft S, Wessendorf JH, Hanau D, Bieber T (1998) Regulation of the high affinity receptor for IgE on human epidermal Langerhans cells. J Immunol 161:1000–1006
McDermott R, Ziylan U, Spehner D, Bausinger H, Lipsker D, Mommaas M, Cazenave JP, Raposo G, Goud B, de la Salle H, Salamero J, Hanau D (2002) Birbeck granules are subdomains of endosomal recycling compartment in human epidermal langerhans cells, which form where langerin accumulates. Mol Biol Cell 13:317–335
Mohamadzadeh M, Berard F, Essert G, Chalouni C, Pulendran B, Davoust J, Bridges G, Palucka AK, Banchereau J (2001) Interleukin 15 skews monocyte differentiation into dendritic cells with features of Langerhans cells. J Exp Med 194:1013–1020
Riedl E, Stockl J, Majdic O, Scheinecker C, Knapp W, Strobl H (2000a) Ligation of E-cadherin on in vitro-generated immature Langerhans-type dendritic cells inhibits their maturation. Blood 96:4276–4284
Riedl E, Stockl J, Majdic O, Scheinecker C, Rappersberger K, Knapp W, Strobl H (2000b) Functional involvement of E-cadherin in TGF-beta 1-induced cell cluster formation of in vitro developing human Langerhans-type dendritic cells. J Immunol 165:1381–1386
Romani N, Lenz A, Glassel H, Stossel H, Stanzl U, Majdic O, Fritsch P, Schuler G (1989) Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. J Invest Dermatol 93:600–609
Strobl H, Riedl E, Scheinecker C, Bello-Fernandez C, Pickl WF, Rappersberger K, Majdic O, Knapp W (1996) TGF-beta 1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J Immunol 157:1499–1507
Strobl H, Bello-Fernandez C, Riedl E, Pickl WF, Majdic O, Lyman SD, Knapp W (1997) flt3 ligand in cooperation with transforming growth factor-beta1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions. Blood 90:1425–1434
Tang A, Amagai M, Granger LG, Stanley J R, Udey MC (1993) Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature 361:82–85
Valladeau J, Duvert-Frances V, Pin JJ (1999) The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface. Eur J Immunol 29:2695–2704
Valladeau J, Ravel O, Dezutter-Dambuyant C (2000) Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12:71–81
Acknowledgements
This project was supported by the Forschergruppe 367/1-2 (project 2) and the Sonderforschungsbereich 284 (project C8) of the Deutsche Forschungsgemeinschaft (DFG).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Allam, JP., Geiger, E., Kraft, S. et al. Limited reliability of E-cadherin as a specific marker for in vitro-generated Langerhans cells. Arch Dermatol Res 295, 263–268 (2003). https://doi.org/10.1007/s00403-003-0423-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-003-0423-6