Up-regulation of the chemokine CCL18 by macrophages is a potential immunomodulatory pathway in cutaneous T-cell lymphoma.

Abstract

Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma (CTCL), which can deteriorate from patch stage to dermal-based tumors and systemic involvement in years. The interaction of chemokines in the skin with CTCL cells might have implications for the pathogenesis of the disease. In this study, we show by PCR analysis and immunofluorescence staining that the chemokine CCL18 is present in skin biopsy specimens of patients with MF and its precursor form parapsoriasis en plaque but not in healthy tissue. In addition, the serum levels of CCL18 were increased threefold in MF patients compared with those in healthy controls. In skin, CCL18 was specifically expressed by CD163(+) CD209(+) macrophages at the invasive margin of the tumor and not expressed by mature CD208(+) dendritic cells in the center of the tumor. The chemokine CCL17 was, by contrast, ubiquitously expressed. Furthermore, CCL18 promoted the chemotaxis but not the proliferation of CTCL cells. CCL18 inhibited proliferation of tumor cells and abolished the CXCL12-induced growth of a CTCL cell line. These data link the increased expression of CCL18 with CTCL and suggest an immunomodulatory effect of the chemokine in the pathogenesis of CTCL.

• Authors: Claudia Günther, Nick Zimmermann, Nicole Berndt, Marianne Grosser, Annette Stein, Andre Koch, Michael Meurer
• Journal: The American journal of pathology (Am J Pathol) Vol. 179 Issue 3 Pg. 1434-42 (Sep 2011) ISSN: 1525-2191 [Electronic] United States
• PMID: 21741937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• CCL18 protein, human
• Chemokines, CC
• Immunologic Factors
• RNA, Messenger

Topics

• Aged
• Aged, 80 and over
• Antigens, CD (metabolism)
• Biopsy
• Cell Line, Tumor
• Chemokines, CC (metabolism)
• Dendritic Cells (metabolism)
• Female
• Humans
• Immunologic Factors
• Lymphoma, T-Cell, Cutaneous (blood, pathology)
• Macrophages (metabolism)
• Male
• RNA, Messenger (metabolism)
• Skin Neoplasms (blood, pathology)
• Up-Regulation