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

Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma

“…TOX (Thymocyte selectionassociated high mobility group box) and EVA1 (Epithelial C-like antigen 1) are usually expressed in thymocyte development, but are subsequently downregulated in mature T cells, 25,26 while BLK (B-lymphoid kinase) and POU2AF are usually specific to B cells and should not be expressed in T cells. 27,28 PLS3 (Plastin 3) is an actin binding protein, which is also normally not expressed in T cells.…”

Comparison of CD163+ CD206+ M2 Macrophages in the Lesional Skin of Bullous Pemphigoid and Pemphigus Vulgaris: The Possible Pathogenesis of Bullous Pemphigoid

“…Recently, Günther et al [1] suggested that there is a relationship between the CCL18 serum levels and the course of the disease in patients with chronic BP. More recently, in another report, Günther et al [10] suggested that, in patients with mycosis fungoides, one of the potential producers of CCL18 is the CD163+ macrophage. In sum, CCL18 from M2 macrophages should be one of the prognostic factors for BP.…”

“…M2 macrophages have important roles in the response to parasite infection, tissue remodeling, angiogenesis and tumor progression, and have been shown to be involved in Th2 polarization [8]. Previous reports suggested that in patients with mycosis fungoides, M2 macrophages could be among the producers of CCL18, the increased expression of which is associated with the disease severity and prognosis [9,10]. Interestingly, in patients with BP, the serum CCL18 levels are also elevated, which might contribute to the disease course [1].…”

Association of the numbers of CD163+ cells in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma

“…Dermal macrophages are a possible source of these cytokines/chemokines. CD163 + cells were detected in the invasive margin of the tumor in CTCL patients [26]. Moreover, abundant CD163 + cells were observed intermingled among tumor cells in a murine cutaneous lymphoma model [27].…”