Mycosis Fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL) is characterized by a helper T cell 2 (Th2)-skewing with a mature CD4+ memory T-cell phenotype. Using skin samples from MF patients (n=21), healthy volunteers (n=17), individuals with atopic dermatitis (n=17) and psoriasis (n=9), we found interleukin (IL)-32 mRNA expression significantly higher in MF samples than in samples from benign inflammatory skin diseases, and its expression increases with disease progression. By immunohistochemistry and immunofluorescence, we confirmed IL-32 protein expression in many CD3+CD4+ T cells and some epidermotropic T cells in MF lesions. MyLa cells (a MF cell line) express IL-32, which in turn could promote cellular proliferation and viability in a dose-dependent fashion. IL-32-treated MyLa and CTCL HH cells up-regulated cell proliferation and survival genes. Of the major "polarizing" T-cell cytokines, only IFNγ mRNA increases with MF progression and positively correlates with IL-32 mRNA expression. Th2 cytokines do not positively correlate with IL-32 mRNA expression or MF progression. Furthermore, by flow cytometry, IL-32 production by circulating activated T-cells in healthy individuals was found in both IFNγ+ and IFNγ- cells but not in IL-4+ or IL-13+ cells. In conclusion, we have identified IL-32+ cells as the likely tumor cells in MF, and demonstrated that IL-32 mRNA expression increases with MF progression and is significantly higher than those in other skin diseases, and that some IL-32+ T cells are independent from the defined Th subsets. Thus IL-32 may play a unique role in MF progression as an autocrine cytokine.
- Received November 11, 2013.
- Revision received May 28, 2014.
- Accepted May 29, 2014.
- Copyright © 2014, American Association for Cancer Research.