Abstract
AbstractEpithelial Langerhans cells (LC) represent immature dendritic cells that require TGF-β1 stimulation for their development. Little is known about the mechanisms regulating LC generation from their precursor cells. We demonstrate here that LC development from human CD34+ hemopoietic progenitor cells in response to TGF-β1 costimulation (basic cytokine combination GM-CSF plus TNF-α, stem cell factor, and Flt3 ligand) is associated with pronounced cell cluster formation of developing LC precursor cells. This cell-clustering phenomenon requires hemopoietic progenitor cell differentiation, since it is first seen on day 4 after culture initiation of CD34+ cells. Cell cluster formation morphologically indicates progenitor cell development along the LC pathway, because parallel cultures set up in the absence of exogenous TGF-β1 fail to form cell clusters and predominantly give rise to monocyte, but not LC, development (CD1a−, lysozyme+, CD14+). TGF-β1 costimulation of CD34+ cells induces neoexpression of the homophilic adhesion molecule E-cadherin in the absence of the E-cadherin heteroligand CD103. Addition of anti-E-cadherin mAb or mAbs to any of the constitutively expressed adhesion molecule (CD99, CD31, LFA-1, or CD18) to TGF-β1-supplemented progenitor cell cultures inhibits LC precursor cell cluster formation, and this effect is, with the exception of anti-E-cadherin mAb, associated with inhibition of LC generation. Addition of anti-E-cadherin mAb to the culture allows cell cluster-independent generation of LC from CD34+ cells. Thus, functional E-cadherin expression and homotypic cell cluster formation represent a regular response of LC precursor cells to TGF-β1 stimulation, and cytoadhesive interactions may modulate LC differentiation from hemopoietic progenitor cells.
Bibliography
Riedl, E., StoÌckl, J., Majdic, O., Scheinecker, C., Rappersberger, K., Knapp, W., & Strobl, H. (2000). Functional Involvement of E-Cadherin in TGF-β1-Induced Cell Cluster Formation of In Vitro Developing Human Langerhans-Type Dendritic Cells. The Journal of Immunology, 165(3), 1381â1386.
References
46
Referenced
54
-
Steinman, R.. 1991. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9: 271
(
10.1146/annurev.iy.09.040191.001415
) - Udey, M. C.. 1997. Cadherins and Langerhans cell immunobiology. Clin. Exp. Immunol. 107: (Suppl. 1):6
-
Strobl, H., E. Riedl, C. Bello-Fernandez, W. Knapp. 1998. Epidermal Langerhans cell development and differentiation. Immunobiology 198: 588
(
10.1016/S0171-2985(98)80080-6
) -
Tang, A., M. Amagai, L. G. Granger, J. R. Stanley, M. C. Udey. 1993. Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature 361: 82
(
10.1038/361082a0
) -
Blauvelt, A., S. I. Katz, M. C. Udey. 1995. Human Langerhans cells express E-cadherin. J. Invest. Dermatol. 104: 293
(
10.1111/1523-1747.ep12612830
) -
Jakob, T., A. Saitoh, M. C. Udey. 1997. E-cadherin-mediated adhesion involving Langerhans cell-like dendritic cells expanded from murine fetal skin. J. Immunol. 159: 2693
(
10.4049/jimmunol.159.6.2693
) -
Borkowski, T. A., B. J. Van Dyke, K. Schwarzenberger, V. W. McFarland, A. G. Farr, M. C. Udey. 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
(
10.1002/eji.1830241129
) -
Schwarzenberger, K., M. C. Udey. 1996. Contact allergens and epidermal proinflammatory cytokines modulate Langerhans cell E-cadherin expression in situ. J. Invest. Dermatol. 106: 553
(
10.1111/1523-1747.ep12344019
) -
Lee, M.-G., S. O. Sharrow, A. G. Farr, A. Singer, M. C. Udey. 1994. Expression of the homophilic adhesion molecule E-cadherin by immature thymocytes and thymic epithelial cells. J. Immunol. 152: 5653
(
10.4049/jimmunol.152.12.5653
) -
Muller, K. M., C. J. Luedecker, M. C. Udey, A. G. Farr. 1997. Involvement of E-cadherin in thymus organogenesis and thymocyte maturation. Immunity 6: 257
(
10.1016/S1074-7613(00)80328-3
) - Lee, M. G., A. Tang, S. O. Sharrow, M. C. Udey. 1994. Murine dendritic epidermal T cells (DETC) express the homophilic adhesion molecule E-cadherin. Epithelial Cell Biol. 3: 149
-
Armeanu, S., H.-J. Bühring, M. Reuss-Borst, C. A. Müller, G. Klein. 1995. E-cadherin is functionally involved in the maturation of the erythroid lineage. J. Cell Biol. 131: 243
(
10.1083/jcb.131.1.243
) -
Strobl, H., E. Riedl, C. Scheinecker, C. Bello-Fernandez, W. F. Pickl, K. Rappersberger, O. Majdic, W. Knapp. 1996. TGF-β1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J. Immunol. 157: 1499
(
10.4049/jimmunol.157.4.1499
) -
Borkowski, T. A., J. J. Letterio, A. G. Farr, M. C. Udey. 1996. A role for endogenous transforming growth factor β 1 in Langerhans cell biology: the skin of transforming growth factor β1 null mice is devoid of epidermal Langerhans cells. J. Exp. Med. 184: 2417
(
10.1084/jem.184.6.2417
) -
Borkowski, T. A., J. J. Letterio, C. L. Mackall, A. Saitoh, X.-J. Wang, D. R. Roop, R. E. Gress, M. C. Udey. 1997. A role for TGFβ1 in Langerhans cell biology. J. Clin. Invest. 100: 575
(
10.1172/JCI119567
) - Boivin, G. P., B. A. O’Toole, I. E. Orsmby, R. J. Diebold, M. J. Eis, T. Doetschman, A. B. Kier. 1995. Onset and progression of pathological lesions in transforming growth factor-β1-deficient mice. Am. J. Pathol. 146: 276
-
Gruschwitz, M. S., O. P. Hornstein. 1992. Expression of transforming growth factor type β on human epidermal dendritic cells. J. Invest. Dermatol. 99: 114
(
10.1111/1523-1747.ep12611890
) -
de Saint-Vis, B., I. Fugier-Vivier, C. Massacrier, C. Gaillard, B. Vanbervliet, S. Ait-Yahia, J. Banchereau, Y. J. Liu, S. Lebecque, C. Caux. 1998. The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation. J. Immunol. 160: 1666
(
10.4049/jimmunol.160.4.1666
) -
Lee, W. C., C. Zhong, S. Qian, Y. Wan, J. Gauldie, Z. Mi, P. D. Robbins, A. W. Thomson, L. Lu. 1998. Phenotype, function, and in vivo migration and survival of allogeneic dendritic cell progenitors genetically engineered to express TGF-β. Transplantation 66: 1810
(
10.1097/00007890-199812270-00040
) -
Majdic, O., J. Stöckl, W. F. Pickl, J. Bohuslav, H. Strobl, C. Scheinecker, H. Stockinger, W. Knapp. 1994. Signaling and induction of enhanced cytoadhesiveness via the hematopoietic progenitor cell surface molecule CD34. Blood 83: 1226
(
10.1182/blood.V83.5.1226.1226
) -
Waclavicek, M., O. Majdic, T. Stulnig, M. Berger, R. Sunder-Plassmann, G. J. Zlabinger, T. Baumruker, J. Stoeckl, C. Ebner, W. Knapp, et al 1998. CD99 engagement on human peripheral blood T cells results in TCR/CD3 dependent cellular activation and allows for Th1-restricted cytokine production. J. Immunol. 161: 4671
(
10.4049/jimmunol.161.9.4671
) -
Smith, C. W., R. Rothlein, B. J. Hughes, M. M. Mariscalco, H. E. Rudloff, F. C. Schmalstieg, D. C. Anderson. 1988. Recognition of an endothelial determinant for CD18-dependent human neutrophil adherence and transendothelial migration. J. Clin. Invest. 82: 1746
(
10.1172/JCI113788
) -
Davis, L. S., N. Oppenheimer-Marks, J. L. Bednarczyk, B. W. McIntyre, P. E. Lipsky. 1990. Fibronectin promotes proliferation of naive and memory T cells by signaling through both the VLA-4 and VLA-5 integrin molecules. J. Immunol. 145: 785
(
10.4049/jimmunol.145.3.785
) -
Weller, P. F., T. H. Rand, S. E. Goelz, G. Chi-Rosso, R. R. Lobb. 1991. Human eosinophil adherence to vascular endothelium mediated by binding to vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule 1. Proc. Natl. Acad. Sci. USA 88: 7430
(
10.1073/pnas.88.16.7430
) - Blase, L., A. Merling, S. Engelmann, P. Moller, R. Schwartz-Albiez. 1996. Characterization of cell surface-expressed proteochondroitin sulfate of pre-B Nalm-6 cells and its possible role in laminin adhesion. Leukemia 10: 1000
- Shimoyama, Y., S. Hirohashi, S. Hirano, M. Noguchi, Y. Shimosato, M. Takeichi, O. Abe. 1989. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 49: 2128
-
Lastres, P., N. Almendro, T. Bellon, J. A. Lopez-Guerrero, R. Eritja, C. Bernabeu. 1994. Functional regulation of platelet/endothelial cell adhesion molecule-1 by TGF-β1 in promonocytic U-937 cells. J. Immunol. 153: 4206
(
10.4049/jimmunol.153.9.4206
) -
Stöckl, J., O. Majdic, W. F. Pickl, A. Rosenkranz, E. Prager, E. Gschwantler, W. Knapp. 1995. Granulocyte activation via a binding site near the C-terminal region of complement receptor type 3 α-chain (CD11b) potentially involved in intramembrane complex formation with glycosylphophatidylinositol-anchored FcγRIIIB (CD16) molecules. J. Immunol. 154: 5452
(
10.4049/jimmunol.154.10.5452
) -
Strobl, H., C. Bello-Fernandez, E. Riedl, W. F. Pickl, O. Majdic, S. T. Lyman, W. Knapp. 1997. Flt3 ligand in cooperation with transforming growth factor-β1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions. Blood 90: 1425
(
10.1182/blood.V90.4.1425
) -
Caux, C., B. Vanbervliet, C. Massacrier, C. Dezutter-Dambuyant, B. de Saint-Vis, C. Jacquet, K. Yoneda, S. Imamura, D. Schmitt, J. Banchereau. 1996. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNFα. J. Exp. Med. 184: 695
(
10.1084/jem.184.2.695
) -
Szabolcs, P., M. A. S. Moore, J. W. Young. 1995. Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured with c-Kit ligand, granulocyte-macrophage colony-stimulating factor, and TNF α. J. Immunol. 154: 5851
(
10.4049/jimmunol.154.11.5851
) -
Maraskovsky, E., K. Brasel, M. Teepe, E. R. Roux, S. D. Lyman, K. Shortman, H. J. McKenna. 1996. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J. Exp. Med. 184: 1953
(
10.1084/jem.184.5.1953
) -
Cepek, K. L., S. K. Shaw, C. M. Parker, G. J. Russell, J. S. Morrow, D. L. Rimm, M. B. Brenner. 1994. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin. Nature 372: 190
(
10.1038/372190a0
) -
Knapp, W., H. Strobl, C. Scheinecker, C. Bello-Fernandez, O. Majdic. 1995. Molecular characterization of CD34+ human hematopoietic progenitor cells. Ann. Hematol. 70: 281
(
10.1007/BF01696614
) -
Scheinecker, C., H. Strobl, G. Fritsch, B. Csmarits, O. Krieger, O. Majdic, W. Knapp. 1995. Granulomonocyte-associated lysosomal protein expression during in vitro expansion and differentiation of CD34+ hemopoietic progenitor cells. Blood 86: 4115
(
10.1182/blood.V86.11.4115.bloodjournal86114115
) -
Riedl, E., H. Strobl, O. Majdic, W. Knapp. 1997. TGF-β1 promotes in vitro generation of dendritic cells by protecting progenitor cells from apoptosis. J. Immunol. 158: 1591
(
10.4049/jimmunol.158.4.1591
) -
Geissmann, F., C. Prost, J. P. Monnet, M. Dy, N. Brousse, O. Hermine. 1998. Transforming growth factor β1, 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
(
10.1084/jem.187.6.961
) -
Jaksits, S., E. Kriehuber, A. S. Charbonnier, K. Rappersberger, G. Stingl, D. Maurer. 1999. CD34+ cell-derived CD14+ precursor cells develop into Langerhans cells in a TGF-β1-dependent manner. J. Immunol. 163: 4869
(
10.4049/jimmunol.163.9.4869
) -
Caux, C., C. Massacrier, B. Dubois, J. Valladeau, C. Dezutter-Dambuyant, I. Durand, D. Schmitt, S. Saeland. 1999. Respective involvement of TGF-β and IL-4 in the development of Langerhans cells and non-Langerhans dendritic cells from CD34+ progenitors. J. Leukocyte Biol. 66: 781
(
10.1002/jlb.66.5.781
) -
Kim, S. H., E. Y. Choi, Y. K. Shin, T. J. Kim, D. H. Chung, S. I. Chang, N. K. Kim, S. H. Park. 1998. Generation of cells with Hodgkin’s and Reed-Sternberg phenotype through downregulation of CD99 (Mic2). Blood 92: 4287
(
10.1182/blood.V92.11.4287
) -
Yong, K. L., M. Watts, N. Shaun Thomas, A. Sullivan, S. Ings, D. C. Linch. 1998. Transmigration of CD34+ cells across specialized and nonspecialized endothelium requires prior activation by growth factors and is mediated by PECAM-1 (CD31). Blood 91: 1196
(
10.1182/blood.V91.4.1196
) -
Ferrero, E., A. Bodanza, B. E. Leone, S. Mancini, A. Poggi, M. R. Zocchi. 1998. CD14+ CD34+ peripheral blood mononuclear cells migrate across endothelium and give rise to immunostimulatory dendritic cells. J. Immunol. 160: 2675
(
10.4049/jimmunol.160.6.2675
) -
Larue, L., C. Antos, S. Butz, O. Huber, V. Delmas, M. Dominis, R. Kemler. 1996. A role for cadherins in tissue formation. Development 122: 3185
(
10.1242/dev.122.10.3185
) -
Kinch, M. S., L. Petch, C. Zhong, K. Burridge. 1997. E-cadherin engagement stimulates tyrosine phosphorylation. Cell. Adhes. Commun. 4: 425
(
10.3109/15419069709004459
) -
Levenberg, S., B. Z. Katz, K. M. Yamada, and B. Geiger. 1998. Long-range and selective autoregulation of cell-cell or cell-matrix adhesions by cadherin or integrin ligands. J. Cell. Sci. 111.
(
10.1242/jcs.111.3.347
) -
Levenberg, S., A. Yarden, Z. Kam, B. Geiger. 1999. p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. Oncogene 18: 869
(
10.1038/sj.onc.1202396
)
Dates
Type | When |
---|---|
Created | 11 years, 4 months ago (April 22, 2014, 5:16 p.m.) |
Deposited | 8 months ago (Jan. 2, 2025, 1:01 p.m.) |
Indexed | 5 months ago (April 6, 2025, 5:03 p.m.) |
Issued | 25 years, 1 month ago (Aug. 1, 2000) |
Published | 25 years, 1 month ago (Aug. 1, 2000) |
Published Print | 25 years, 1 month ago (Aug. 1, 2000) |
@article{Riedl_2000, title={Functional Involvement of E-Cadherin in TGF-β1-Induced Cell Cluster Formation of In Vitro Developing Human Langerhans-Type Dendritic Cells}, volume={165}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.165.3.1381}, DOI={10.4049/jimmunol.165.3.1381}, number={3}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Riedl, Elisabeth and Stöckl, Johannes and Majdic, Otto and Scheinecker, Clemens and Rappersberger, Klemens and Knapp, Walter and Strobl, Herbert}, year={2000}, month=aug, pages={1381–1386} }