title: IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF).
abstract: Skin lesions from mycosis fungoides (MF) patients display an increased expression of interleukin-15 (IL-15), IL-17F, and other cytokines implicated in inflammation and malignant cell proliferation in cutaneous T-cell lymphoma (CTCL). In the leukemic variant of CTCL, Sézary syndrome (SS), IL-2 and IL-15 trigger activation of the Jak-3/STAT3 pathway and transcription of IL17A gene, whereas it is unknown what causes IL-15 expression, Jak3/STAT3 activation, and production of IL-17F in MF. Here, we studied the expression and regulation of IL-15 and its relation to IL-17F in MF cell lines and skin lesions from 60 MF patients. We show that: (1) the spontaneous IL-15 mRNA expression is resistant to Jak3 and STAT3 inhibitors at concentrations that profoundly inhibit STAT3 activation and IL-17F mRNA expression; (2) anti-IL-15 antibody blocks STAT3 activation induced by exogenous IL-15 in non-malignant MF T cells, whereas the spontaneous STAT3 activation and IL-17F expression in malignant T cells is not inhibited; (3) patients display heterogeneous IL-15/IL-17F mRNA expression patterns in skin lesions; and (4) IL-15 expression (in contrast to IL-17F) is not associated with progressive disease. Taken together, these findings indicate that IL-15 and IL-17F are differentially regulated and expressed in MF. We propose that IL-15 and IL-17F are markers for different inflammatory environments and play distinct roles in the development and progression of MF.
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Willerslev-Olsen
authors.affiliation: Division of Dermatology; McGill University Health Centre; Montréal, Quebec, Canada.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Litvinov
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Fredholm
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: David L
authors.initials: DL
authors.lastname: Petersen
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: Nina A
authors.initials: NA
authors.lastname: Sibbesen
authors.affiliation: Departmen of Dermatology; Copenhagen University Hospital; Bispebjerg, Copenhagen, Denmark.
authors.forename: Robert
authors.initials: R
authors.lastname: Gniadecki
authors.affiliation: Department of Pathology and Laboratory Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.affiliation: Department of Pathology and Laboratory Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.affiliation: Department of Dermatology and Skin Science; University of British Columbia; Vancouver, British Columbia, Canada.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.affiliation: Division of Dermatology; McGill University Health Centre; Montréal, Quebec, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Sasseville
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.affiliation: Department of International Health, Immunology, and Microbiology; University of Copenhagen; Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism* / Q000473:pathology; D009182:Mycosis Fungoides / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D019409:Interleukin-15; D020381:Interleukin-17; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: CTCL; IL-15; IL-17F; Jak3; MF; STAT3