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/CCL20 and CC Chemokine Receptor 6 in Psoriasis1
*
DNAX Research Institute, Palo Alto, CA 94304;
Laboratory for Immunological Research, Schering Plough, Dardilly, France;
Department of Dermatology, Heinrich Heine University, Dusseldorf, Germany; and
§
Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico
Autoimmunity plays a key role in the immunopathogenesis of
psoriasis; however, little is known about the recruitment of pathogenic
cells to skin lesions. We report here that the CC chemokine, macrophage
inflammatory protein-3
, recently renamed CCL20, and its receptor
CCR6 are markedly up-regulated in psoriasis. CCL20-expressing
keratinocytes colocalize with skin-infiltrating T cells in lesional
psoriatic skin. PBMCs derived from psoriatic patients show
significantly increased CCR6 mRNA levels. Moreover, skin-homing
CLA+ memory T cells express high levels of surface CCR6.
Furthermore, the expression of CCR6 mRNA is 100- to 1000-fold higher on
sorted CLA+ memory T cells than other chemokine receptors,
including CXCR1, CXCR2, CXCR3, CCR2, CCR3, and CCR5. In vitro, CCL20
attracted skin-homing CLA+ T cells of both normal and
psoriatic donors; however, psoriatic lymphocytes responded to lower
concentrations of chemokine and showed higher chemotactic responses.
Using ELISA as well as real-time quantitative PCR, we show that
cultured primary keratinocytes, dermal fibroblasts, and dermal
microvascular endothelial and dendritic cells are major sources of
CCL20, and that the expression of this chemokine can be induced by
proinflammatory mediators such as TNF-/IL-1ß, CD40 ligand,
IFN-
, or IL-17. Taken together, these findings strongly suggest that
CCL20/CCR6 may play a role in the recruitment of T cells to lesional
psoriatic skin.
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D. M. Hoover, C. Boulegue, D. Yang, J. J. Oppenheim, K. Tucker, W. Lu, and J. Lubkowski The Structure of Human Macrophage Inflammatory Protein-3alpha /CCL20. LINKING ANTIMICROBIAL AND CC CHEMOKINE RECEPTOR-6-BINDING ACTIVITIES WITH HUMAN beta -DEFENSINS J. Biol. Chem., September 27, 2002; 277(40): 37647 - 37654. [Abstract] [Full Text] [PDF]
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W. Maki, R. E. Morales, V. A. Carroll, W. G. Telford, R. N. Knibbs, L. M. Stoolman, and S. T. Hwang CCR6 Colocalizes with CD18 and Enhances Adhesion to Activated Endothelial Cells in CCR6-Transduced Jurkat T Cells J. Immunol., September 1, 2002; 169(5): 2346 - 2353. [Abstract] [Full Text] [PDF]
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B.-C. Chiu, X.-Z. Shang, V. R. Stolberg, E. Komuniecki, and S. W. Chensue Population analysis of CD4+ T cell chemokine receptor transcript expression during in vivo type-1 (mycobacterial) and type-2 (schistosomal) immune responses J. Leukoc. Biol., August 1, 2002; 72(2): 363 - 372. [Abstract] [Full Text] [PDF]
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S. Hudak, M. Hagen, Y. Liu, D. Catron, E. Oldham, L. M. McEvoy, and E. P. Bowman Immune Surveillance and Effector Functions of CCR10+ Skin Homing T Cells J. Immunol., August 1, 2002; 169(3): 1189 - 1196. [Abstract] [Full Text] [PDF]
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S. Sugita, T. Kohno, K. Yamamoto, Y. Imaizumi, H. Nakajima, T. Ishimaru, and T. Matsuyama Induction of Macrophage-Inflammatory Protein-3{alpha} Gene Expression by TNF-Dependent NF-{kappa}B Activation J. Immunol., June 1, 2002; 168(11): 5621 - 5628. [Abstract] [Full Text] [PDF]
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G. Page, S. Lebecque, and P. Miossec Anatomic Localization of Immature and Mature Dendritic Cells in an Ectopic Lymphoid Organ: Correlation with Selective Chemokine Expression in Rheumatoid Synovium J. Immunol., May 15, 2002; 168(10): 5333 - 5341. [Abstract] [Full Text] [PDF]
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 Y. Imaizumi, S. Sugita, K. Yamamoto, D. Imanishi, T. Kohno, M. Tomonaga, and T. Matsuyama Human T cell leukemia virus type-I Tax activates human macrophage inflammatory protein-3{alpha}/CCL20 gene transcription via the NF-{kappa}B pathway Int. Immunol., February 1, 2002; 14(2): 147 - 155. [Abstract] [Full Text] [PDF]
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S. Aggarwal and A. L. Gurney IL-17: prototype member of an emerging cytokine family J. Leukoc. Biol., January 1, 2002; 71(1): 1 - 8. [Abstract] [Full Text] [PDF]
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L. M. Ebert and S. R. McColl Up-Regulation of CCR5 and CCR6 on Distinct Subpopulations of Antigen-Activated CD4+ T Lymphocytes J. Immunol., January 1, 2002; 168(1): 65 - 72. [Abstract] [Full Text] [PDF]
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A. Y. Savinov, F. S. Wong, and A. V. Chervonsky IFN-{gamma} Affects Homing of Diabetogenic T Cells J. Immunol., December 1, 2001; 167(11): 6637 - 6643. [Abstract] [Full Text] [PDF]
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M.-C. Dieu-Nosjean, C. Massacrier, B. Vanbervliet, W.-H. Fridman, and C. Caux IL-10 Induces CCR6 Expression During Langerhans Cell Development While IL-4 and IFN-{gamma} Suppress It J. Immunol., November 15, 2001; 167(10): 5594 - 5602. [Abstract] [Full Text] [PDF]
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M. Chabaud, G. Page, and P. Miossec Enhancing Effect of IL-1, IL-17, and TNF-{alpha} on Macrophage Inflammatory Protein-3{alpha} Production in Rheumatoid Arthritis: Regulation by Soluble Receptors and Th2 Cytokines J. Immunol., November 15, 2001; 167(10): 6015 - 6020. [Abstract] [Full Text] [PDF]
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A. Pardo, K. M. Smith, J. Abrams, R. Coffman, M. Bustos, T. K. McClanahan, J. Grein, E. E. Murphy, A. Zlotnik, and M. Selman CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis J. Leukoc. Biol., October 1, 2001; 70(4): 610 - 616. [Abstract] [Full Text] [PDF]
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S. Fujiie, K. Hieshima, D. Izawa, T. Nakayama, R. Fujisawa, H. Ohyanagi, and O. Yoshie Proinflammatory cytokines induce liver and activation-regulated chemokine/macrophage inflammatory protein-3{alpha}/CCL20 in mucosal epithelial cells through NF-{kappa}B Int. Immunol., October 1, 2001; 13(10): 1255 - 1263. [Abstract] [Full Text] [PDF]
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C. W. Cutler, R. Jotwani, and B. Pulendran Dendritic Cells: Immune Saviors or Achilles' Heel? Infect. Immun., August 1, 2001; 69(8): 4703 - 4708. [Full Text] [PDF]
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T. Nakayama, R. Fujisawa, H. Yamada, T. Horikawa, H. Kawasaki, K. Hieshima, D. Izawa, S. Fujiie, T. Tezuka, and O. Yoshie Inducible expression of a CC chemokine liver- and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3{{alpha}}/CCL20 by epidermal keratinocytes and its role in atopic dermatitis Int. Immunol., January 1, 2001; 13(1): 95 - 103. [Abstract] [Full Text] [PDF]
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D. J. Fitzhugh, S. Naik, S. W. Caughman, and S. T. Hwang Cutting Edge: C-C Chemokine Receptor 6 Is Essential for Arrest of a Subset of Memory T Cells on Activated Dermal Microvascular Endothelial Cells Under Physiologic Flow Conditions In Vitro J. Immunol., December 15, 2000; 165(12): 6677 - 6681. [Abstract] [Full Text] [PDF]
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M.-C. Dieu-Nosjean, C. Massacrier, B. Homey, B. Vanbervliet, J.-J. Pin, A. Vicari, S. Lebecque, C. Dezutter-Dambuyant, D. Schmitt, A. Zlotnik, et al. Macrophage Inflammatory Protein 3{alpha} Is Expressed at Inflamed Epithelial Surfaces and Is the Most Potent Chemokine Known in Attracting Langerhans Cell Precursors J. Exp. Med., September 5, 2000; 192(5): 705 - 718. [Abstract] [Full Text] [PDF]
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