Abstract
Plasmacytoid dendritic cell (PDC) leukemia/lymphoma is a rare neoplasm presenting cutaneous lesions at the time of diagnosis, followed by dissemination to bone marrow, lymph nodes, and other lymphoid and nonlymphoid organs. Since these leukemic counterparts of human PDC are similar to normal PDC, we studied their chemokine receptor equipment and their migratory capacities. We found both in skin lesions and in invaded lymph nodes an expression by tumor cells of CXCR3, CXCR4, and CCR7, and the concomitant expression by cells in the microenvironment of their respective ligands CXCL9, CXCL12, and CCL19. Moreover, flow cytometry phenotype of leukemic PDC (LPDC) revealed an unexpected expression of CCR6. We show that fresh tumor cells are able to migrate in response to CXCR4, CCR2, CCR5, CCR6, and CCR7 ligands, and the ability of CXCR3 ligands to increase the responsiveness to CXCL12. IL-3- or virus-induced activation of LPDC leads to downregulation of CXCR3 and CXCR4, and upregulation of CCR7, associated with the loss of response to CXCL12, and the acquisition of sensitivity to CCL19. Altogether, these results suggest that the preferential accumulation of LPDC in the skin or lymph nodes could be orchestrated by CXCR3, CXCR4, CCR6, and CCR7 ligands, found in nontumoral structures of invaded organs.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Dieu-Nosjean MC, Vicari A, Lebecque S, Caux C . Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines. J Leukoc Biol 1999; 66: 252–262.
Vanbervliet B, Homey B, Durand I, Massacrier C, Ait-Yahia S, de Bouteiller O et al. Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces. Eur J Immunol 2002; 32: 231–242.
Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Ait-Yahia S et al. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med 1998; 188: 373–386.
Sallusto F, Schaerli P, Loetscher P, Schaniel C, Lenig D, Mackay CR et al. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol 1998; 28: 2760–2769.
Sozzani S, Allavena P, Damico G, Luini W, Bianchi G, Kataura M et al. Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties. J Immunol 1998; 161: 1083–1086.
Penna G, Sozzani S, Adorini L . Cutting edge: selective usage of chemokine receptors by plasmacytoid dendritic cells. J Immunol 2001; 167: 1862–1866.
Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 1999; 5: 919–923.
Fonteneau JF, Gilliet M, Larsson M, Dasilva I, Munz C, Liu YJ et al. Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity. Blood 2003; 2: 2.
O'Doherty U, Peng M, Gezelter S, Swiggard WJ, Betjes M, Bhardwaj N et al. Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. Immunology 1994; 82: 487–493.
Olweus J, BitMansour A, Warnke R, Thompson PA, Carballido J, Picker LJ et al. Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin. Proc Natl Acad Sci USA 1997; 94: 12551–12556.
Blom B, Ho S, Antonenko S, Liu YJ . Generation of interferon alpha-producing predendritic cell (Pre-DC)2 from human CD34(+) hematopoietic stem cells. J Exp Med 2000; 192: 1785–1796.
Res PC, Couwenberg F, Vyth Dreese FA, Spits H . Expression of pTalpha mRNA in a committed dendritic cell precursor in the human thymus. Blood 1999; 94: 2647–2657.
Bendriss-Vermare N, Barthelemy C, Durand I, Bruand C, Dezutter-Dambuyant C, Moulian N et al. Human thymus contains IFN-alpha-producing CD11c(−), myeloid CD11c(+), and mature interdigitating dendritic cells. J Clin Invest 2001; 107: 835–844.
Facchetti F, de Wolf-Peeters C, Mason DY, Pulford K, van den Oord JJ, Desmet VJ . Plasmacytoid T cells. Immunohistochemical evidence for their monocyte/macrophage origin. Am J Pathol 1988; 133: 15–21.
Facchetti F, De Wolf-Peeters C, van den Oord JJ, De vos R, Desmet VJ . Plasmacytoid T cells: a cell population normally present in the reactive lymph node. An immunohistochemical and electronmicroscopic study. Hum Pathol 1988; 19: 1085–1092.
Cella M, Facchetti F, Lanzavecchia A, Colonna M . Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. Nat Immunol 2000; 1: 305–310.
Grouard G, Durand I, Filgueira L, Banchereau J, Liu YJ . Dendritic cells capable of stimulating T cells in germinal centres. Nature 1996; 384: 364–367.
Eckert F, Schmid U . Identification of plasmacytoid T cells in lymphoid hyperplasia of the skin. Arch Dermatol 1989; 125: 1518–1524.
Toonstra J, van der Putte SC . Plasmacytoid monocytes in Jessner's lymphocytic infiltration of the skin. A valuable clue for the diagnosis. Am J Dermatopathol 1991; 13: 321–328.
Sellati TJ, Waldrop SL, Salazar JC, Bergstresser PR, Picker LJ, Radolf JD . The cutaneous response in humans to Treponema pallidum lipoprotein analogues involves cellular elements of both innate and adaptive immunity. J Immunol 2001; 166: 4131–4140.
Wollenberg A, Wagner M, Gunther S, Towarowski A, Tuma E, Moderer M et al. Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 2002; 119: 1096–1102.
Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL . Plasmacytoid dendritic cells (natural interferon-alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol 2001; 159: 237–243.
Blomberg S, Eloranta ML, Cederblad B, Nordlin K, Alm GV, Ronnblom L . Presence of cutaneous interferon-alpha producing cells in patients with systemic lupus erythematosus. Lupus 2001; 10: 484–490.
Jahnsen FL, Lund-Johansen F, Dunne JF, Farkas L, Haye R, Brandtzaeg P . Experimentally induced recruitment of plasmacytoid (CD123high) dendritic cells in human nasal allergy. J Immunol 2000; 165: 4062–4068.
Zou W, Machelon V, Coulomb-L'Hermin A, Borvak J, Nome F, Isaeva T et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 2001; 7: 1339–1346.
Krug A, Uppaluri R, Facchetti F, Dorner BG, Sheehan KC, Schreiber RD et al. IFN-producing cells respond to CXCR3 ligands in the presence of CXCL12 and secrete inflammatory chemokines upon activation. J Immunol 2002; 169: 6079–6083.
Pablos JL, Amara A, Bouloc A, Santiago B, Caruz A, Galindo M et al. Stromal-cell derived factor is expressed by dendritic cells and endothelium in human skin. Am J Pathol 1999; 155: 1577–1586.
Piali L, Weber C, LaRosa G, Mackay CR, Springer TA, Clark-Lewis I et al. The chemokine receptor CXCR3 mediates rapid and shear-resistant adhesion-induction of effector T lymphocytes by the chemokines IP10 and Mig. Eur J Immunol 1998; 28: 961–972.
Vanbervliet B, Bendriss-Vermare N, Massacrier C, Homey B, De Bouteiller O, Briere F et al. The inducible CXCR3 ligands control plasmacytoid dendritic cell responsiveness to the constitutive chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12. J Exp Med 2003; 198: 823–830.
Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T et al. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol 2002; 168: 4531–4537.
Jarrossay D, Napolitani G, Colonna M, Sallusto F, Lanzavecchia A . Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol 2001; 31: 3388–3393.
Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 2001; 194: 863–869.
Chaperot L, Bendriss N, Manches O, Gressin R, Maynadie M, Trimoreau F et al. Identification of a leukemic counterpart of the plasmacytoid dendritic cells. Blood 2001; 97: 3210–3217.
Briere F, Bendriss-Vermare N, Delale T, Burg S, Corbet C, Rissoan MC et al. Origin and filiation of human plasmacytoid dendritic cells. Hum Immunol 2002; 63: 1081–1093.
Jacob M-C, Chaperot L, Mossuz P, Feuillard J, Valensi F, Leroux D et al. CD4+ CD56+ lineage negative (lin−) leukemia/lymphoma: a new entity developed from malignant early plasmacytoid dendritic cells (pDC). Hematologica 2003; 88: 941–955.
Feuillard J, Jacob M-C, valensi F, Maynadie M, Gressin R, Chaperot L et al. Clinical and biologic features of CD4+CD56+ malignancies. Blood 2002; 99: 1556–1563.
Leroux D, Mugneret F, Callanan M, Radford-Weiss I, Dastugue N, Feuillard J et al. CD4(+), CD56(+) DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Francais de Cytogenetique Hematologique. Blood 2002; 99: 4154–4159.
Chaperot L, Perrot I, Jacob M-C, Blanchard D, Salaun V, Deneys V et al. Leukemic plasmacytoid dendritic cells share phenotypic and functional features with their normal counterparts. Eur J Immunol 2004; 34: 418–426.
Blades MC, Manzo A, Ingegnoli F, Taylor PR, Panayi GS, Irjala H et al. Stromal cell-derived factor 1 (CXCL12) induces human cell migration into human lymph nodes transplanted into SCID mice. J Immunol 2002; 168: 4308–4317.
Flier J, Boorsma DM, van Beek PJ, Nieboer C, Stoof TJ, Willemze R et al. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. J Pathol 2001; 194: 398–405.
Greaves DR, Wang W, Dairaghi DJ, Dieu MC, Saint-Vis B, Franz-Bacon K et al. CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells. J Exp Med 1997; 186: 837–844.
Charbonnier AS, Kohrgruber N, Kriehuber E, Stingl G, Rot A, Maurer D . Macrophage inflammatory protein 3alpha is involved in the constitutive trafficking of epidermal Langerhans cells. J Exp Med 1999; 190: 1755–1768.
Dieu-Nosjean MC, Massacrier C, Homey B, Vanbervliet B, Pin JJ, Vicari A et al. Macrophage inflammatory protein 3alpha is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors. J Exp Med 2000; 192: 705–718.
Soler D, Humphreys TL, Spinola SM, Campbell JJ . CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking. Blood 2003; 101: 1677–1682.
Katou F, Ohtani H, Nakayama T, Nagura H, Yoshie O, Motegi K . Differential expression of CCL19 by DC-Lamp+ mature dendritic cells in human lymph node versus chronically inflamed skin. J Pathol 2003; 199: 98–106.
Acknowledgements
We are grateful to Laurence Grossi for her technical assistance. We thank Drs Véronique Deneys (UCL Saint Luc, Bruxelles), Rémy Gressin (CHU Grenoble), Emilienne Kuhlein (CHU Toulouse), Marc Maynadié (CHU Dijon), Hubert Orfeuvre (CHR Bourg en Bresse), Véronique Salaün (CHU Caen), and the GEIL (Groupe d'Etude Immunologique des Leucémies) for providing us with tumor cells. We are grateful to Jean-Paul Molens, Olivier Manches, Gabrielle Lui, Juliette Angel, and Ariane Blum for their efficiency in the laboratory. We thank Dr MF Sotto (CHU Grenoble) for help with microscopy. This work was supported by grant nos. 4498 and 4798 from ARC (Association pour la Recherche sur le Cancer), and grant no. 2003.26 from EFS (Etablissement Français du Sang).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bendriss-Vermare, N., Chaperot, L., Peoc'h, M. et al. In situ leukemic plasmacytoid dendritic cells pattern of chemokine receptors expression and in vitro migratory response. Leukemia 18, 1491–1498 (2004). https://doi.org/10.1038/sj.leu.2403452
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2403452
Keywords
This article is cited by
-
Neoplasms derived from plasmacytoid dendritic cells
Modern Pathology (2016)
-
Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition
Leukemia (2014)
-
Plasmacytoid Dendritic Cells in Cutaneous Disorders
Current Dermatology Reports (2013)
-
Characterization of Circulating Dendritic Cells in Melanoma: Role of CCR6 in Plasmacytoid Dendritic Cell Recruitment to the Tumor
Journal of Investigative Dermatology (2010)
-
Skin deep but complex
Nature (2007)