Purpose: Mycosis fungoides (MF), a common type of cutaneous T cell lymphoma with an indolent clinical course, has the characteristic that malignant T cell clones are recruited into the skin from the early disease stages. The mechanisms of recruitment have been suggested from our knowledge of various chemokine-chemokine receptor interactions. Recently, CCR10 and CTACK/CCL27 were proposed to play a role in the recruitment of other types of cutaneous T cell lymphoma. We examined the expression of CCR10 in peripheral blood and serum CTACK/CCL27 levels in patients with MF. Experimental Design: Eighteen patients with MF, six patients with atopic dermatitis, and nine healthy volunteers were enrolled in our investigation. We investigated the differences in CCR10+ CD4+ expression in peripheral blood mononuclear cells by flow cytometry. Serum CTACK/CCL27 levels were determined using a CTACK/CCL27 ELISA assay kit. Results: The number of circulating CCR10+ CD4+ cells was significantly higher in MF peripheral blood than in controls, even during the early stages. In lesional MF skin, infiltrating tumor cells also showed extensive expression of CCR10. The serum level of CTACK/CCL27 was higher in patients with MF than normal controls, but no statistical difference was found compared with atopic dermatitis patients. Conclusions: CCR10-CTACK/CCL27 interactions between circulating T cells and keratinocytes would seem to play an important role in the pathophysiology of MF from the early disease stages.

Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that has an essential role in the pathophysiology of experimental allergic inflammation. Recent findings suggest that MIF is involved in several allergic disorders, including atopic dermatitis (AD). In this study, the role of MIF in allergic skin inflammation was examined using a murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA). We observed the number of skin-infiltrating eosinophils to significantly increase in OVA-sensitized MIF transgenic (Tg) mice compared with their wild-type (WT) littermates. On the other hand, eosinophils were virtually absent from the skin of MIF knockout (KO) mice and failed to infiltrate their skin after repeated epicutaneous sensitization with OVA. The mRNA expression levels of eotaxin and IL-5 were significantly increased in OVA-sensitized skin sites of MIF Tg mice, but were significantly decreased in MIF KO mice in comparison with the levels in WT littermates. Eotaxin expression was induced by IL-4 stimulation in fibroblasts in MIF Tg mice, but not in MIF KO mice. These findings indicate that MIF can induce eosinophil accumulation in the skin. Therefore, the targeted inhibition of MIF might be a promising new therapeutic strategy for allergic skin diseases.

Desmoplastic fibroblastoma (DF) is a rare fibrotic tumor that has a wide anatomic distribution and it can appear in deep sections of the subcutis, in fascia, in aponeurosis or in skeletal muscles. This report describes a case of DF that appeared on the left side of the neck of a 55-year-old male as a 3.5-cm solitary, firm nodule. Histologically, it was composed of stellate or bland spindle-shaped cells embedded in a loose collagenous stroma. The entrapment of fat and muscle tissues was focally identified at the edges of the tumor. The stellate and multinucleated cells in the lesion were strongly positive for vimentin but negative for cytokeratin, smooth muscle actin, desmin, S-100, CD34, factor XIIIa, and CD68. These findings suggest that the stellate and multinucleated cells in the lesion were of fibroblastic origin and this neoplasm was pathologically benign.

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UV radiation indirectly regulates melanogenesis in melanocytes through a paracrine regulatory mechanism involving keratinocytes. Protease-activated receptor (PAR)-2 activation induces melanosome transfer by increasing phagocytosis of melanosomes by keratinocytes. This study demonstrated that macrophage migration inhibitory factor (MIF) stimulated PAR-2 expression in human keratinocytes. In addition, we showed that MIF stimulated stem cell factor (SCF) release in keratinocytes; however, MIF had no effect on the release of endothelin-1 or prostaglandin E2 in keratinocytes. In addition, MIF had no direct effect on melanin and tyrosinase synthesis in cultured human melanocytes. The effect of MIF on melanogenesis was also examined using a three-dimensional reconstituted human epidermal culture model, which is a novel, commercially available, cultured human epidermis containing functional melanocytes. Migration inhibitory factor induced an increase in melanin content in the epidermis after a 9-day culture period. Moreover, melanin synthesis induced by UV-B stimulation was significantly down-regulated by anti-MIF antibody treatment. An in vivo study showed that the back skin of MIF transgenic mice had a higher melanin content than that of wild-type mice after 12 weeks of UV-B exposure. Therefore, MIFmediated melanogenesis occurs mainly through the activation of PAR-2 and SCF expression in keratino- Exposure to UV radiation leads to various short-term deleterious cutaneous effects, including sunburn and immunosuppression, and long-term consequences that lead to premature aging, including hyperpigmentation.1 UV radiation indirectly regulates melanogenesis in melanocytes through a paracrine regulatory mechanism involving keratinocytes. UV-B-induced pigmentation occurs when human keratinocytes exposed to UV-B are stimulated to produce and secrete several mediators that trigger the activation of melanocytes and act as potent mitogens and melanogens for human melanocytes.2-4 The two main paracrine melanogenic cytokines, stem cell factor (SCF) and endothelin (ET)-1, have been demonstrated to play pivotal roles in skin pigmentation, including UV-Binduced pigmentation. 5 In addition, prostaglandins (PGs) are key mediators of diverse functions in the skin; and several reports 6,7 have suggested that PGs mediate postinflammatory pigmentary changes by modulating melanin synthesis and melanocyte dendricity.Protease-activated receptor (PAR)-2 is a member of a novel G-protein-coupled seven-transmembrane receptor family.8 These receptors are irreversibly activated through proteolytic cleavage of their amino termini. Subsequent to proteolytic cleavage, the newly exposed NH2 terminus acts as a tethered peptide ligand, which binds and activates the receptor. Protease-activated receptor-2 is involved in skin pigmentation because it increases the phagocytosis of melanosomes by keratinocytes.9 UV ir-