title: IL32 is progressively expressed in mycosis fungoides independent of helper T-cell 2 and helper T-cell 9 polarization.
abstract: Mycosis fungoides, 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 patients with mycosis fungoides (n = 21), healthy volunteers (n = 17), and individuals with atopic dermatitis (n = 17) and psoriasis (n = 9), we found IL32 mRNA expression significantly higher in mycosis fungoides samples than in samples from benign inflammatory skin diseases, and its expression increases with disease progression. By IHC and immunofluorescence, we confirmed IL32 protein expression in many CD3(+)CD4(+) T cells and some epidermotropic T cells in mycosis fungoides lesions. MyLa cells (a mycosis fungoides cell line) express IL32, which, in turn, could promote cellular proliferation and viability in a dose-dependent fashion. IL32-treated MyLa and CTCL HH cells upregulated cell proliferation and survival genes. Of the major "polarizing" T-cell cytokines, only IFNγ mRNA increases with mycosis fungoides progression and positively correlates with IL32 mRNA expression. Th2 cytokines do not positively correlate with IL32 mRNA expression or mycosis fungoides progression. Furthermore, by flow cytometry, IL32 production by circulating activated T cells in healthy individuals was found in both IFNγ(+) and IFNγ(-) cells but not in IL4(+) or IL13(+) cells. In conclusion, we have identified IL32(+) cells as the likely tumor cells in mycosis fungoides, and demonstrated that IL32 mRNA expression increases with mycosis fungoides progression and is significantly higher than mRNA expression in other skin diseases, and that some IL32(+) T cells are independent from the defined Th subsets. Thus, IL32 may play a unique role in mycosis fungoides progression as an autocrine cytokine.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
authors.forename: Hanako
authors.initials: H
authors.lastname: Ohmatsu
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-University Medical Center Berlin, Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Humme
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Rockefeller University Center for Clinical and Translational Science, New York, New York.
authors.forename: Juana
authors.initials: J
authors.lastname: Gonzalez
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-University Medical Center Berlin, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Möbs
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York. Rockefeller University Center for Clinical and Translational Science, New York, New York.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-University Medical Center Berlin, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York. jgk@rockefeller.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D003876:Dermatitis, Atopic / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D009182:Mycosis Fungoides / Q000276:immunology*; D011565:Psoriasis / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C573415:IFNG protein, human; C496971:IL32 protein, human; D007378:Interleukins; D012333:RNA, Messenger; D007371:Interferon-gamma