IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF)

Andreas Willerslev-Olsen; Ivan V Litvinov; Simon M Fredholm; David L Petersen; Nina A Sibbesen; Robert Gniadecki; Qian Zhang; Charlotte M Bonefeld; Mariusz A Wasik; Carsten Geisler; Youwen Zhou; Anders Woetmann; Denis Sasseville; Thorbjørn Krejsgaard; Niels Ødum

doi:10.4161/cc.28256

IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF)

Andreas Willerslev-Olsen, Ivan V Litvinov, Simon M Fredholm, David L Petersen, Nina A Sibbesen, Robert Gniadecki, Qian Zhang, Charlotte M Bonefeld, Mariusz A Wasik, Carsten Geisler, Youwen Zhou, Anders Woetmann, Denis Sasseville, Thorbjørn Krejsgaard, Niels Ødum

14 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cell Cycle
Vol/bind	13
Udgave nummer	8
Sider (fra-til)	1306-12
Antal sider	7
ISSN	1538-4101
DOI	https://doi.org/10.4161/cc.28256
Status	Udgivet - 15 apr. 2014

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10.4161/cc.28256

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Willerslev-Olsen, A., Litvinov, I. V., Fredholm, S. M., Petersen, D. L., Sibbesen, N. A., Gniadecki, R., Zhang, Q., Bonefeld, C. M., Wasik, M. A., Geisler, C., Zhou, Y., Woetmann, A., Sasseville, D., Krejsgaard, T., & Ødum, N. (2014). IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF). Cell Cycle, 13(8), 1306-12. https://doi.org/10.4161/cc.28256

@article{825f0d3ca5f54083be02ebe62fcf37e5,

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, S{\'e}zary 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.",

author = "Andreas Willerslev-Olsen and Litvinov, {Ivan V} and Fredholm, {Simon M} and Petersen, {David L} and Sibbesen, {Nina A} and Robert Gniadecki and Qian Zhang and Bonefeld, {Charlotte M} and Wasik, {Mariusz A} and Carsten Geisler and Youwen Zhou and Anders Woetmann and Denis Sasseville and Thorbj{\o}rn Krejsgaard and Niels {\O}dum",

year = "2014",

month = apr,

day = "15",

doi = "10.4161/cc.28256",

language = "English",

volume = "13",

pages = "1306--12",

journal = "Cell Cycle",

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TY - JOUR

T1 - IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF)

AU - Willerslev-Olsen, Andreas

AU - Litvinov, Ivan V

AU - Fredholm, Simon M

AU - Petersen, David L

AU - Sibbesen, Nina A

AU - Gniadecki, Robert

AU - Zhang, Qian

AU - Bonefeld, Charlotte M

AU - Wasik, Mariusz A

AU - Geisler, Carsten

AU - Zhou, Youwen

AU - Woetmann, Anders

AU - Sasseville, Denis

AU - Krejsgaard, Thorbjørn

AU - Ødum, Niels

PY - 2014/4/15

Y1 - 2014/4/15

N2 - 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.

AB - 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.

U2 - 10.4161/cc.28256

DO - 10.4161/cc.28256

M3 - Journal article

C2 - 24621498

SN - 1538-4101

VL - 13

SP - 1306

EP - 1312

JO - Cell Cycle

JF - Cell Cycle

IS - 8

ER -

IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF)

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