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Blood, 1 February 2002, Vol. 99, No. 3, pp. 973-977
IMMUNOBIOLOGY
Spontaneous interleukin-5 production in cutaneous T-cell lymphoma
lines is mediated by constitutively activated Stat3
Mette Nielsen,
Mogens H. Nissen,
Jens Gerwien,
Mai-Britt Zocca,
Helene M. Rasmussen,
Koichi Nakajima,
Carsten Röpke,
Carsten Geisler,
Keld Kaltoft, and
Niels Ødum
From the Institute of Medical Microbiology and
Immunology and the Institute of Medical Anatomy, Section A, University
of Copenhagen, Denmark; the Department of Immunology, Osaka City
Medical School, Japan; and Institute of Human Genetics, University of
Aarhus, Denmark.
Mycosis fungoides is a low-grade cutanous T-cell lymphoma
(CTCL) of unknown etiology. In advanced stages of CTCL, a shift in
cytokine profile from TH1 to TH2 is observed,
which coincides with eosinophilia, high levels of immunoglobulin E, and
increased susceptibility to bacterial infections. It is, however,
unknown why TH2 cytokines predominate in advanced CTCL, and
the cellular source of these cytokines also remains to be identified.
In several leukemias and lymphomas, constitutively activated signal
transducer and activator of transcription (Stat) signaling pathways
have been detected. In a previous study, constitutive activation of Stat3 was found in tumor cells isolated from affected skin and blood
from CTCL patients. Here, it is shown that CTCL tumor cell lines, but not nonmalignant cell lines, spontaneously produce interleukin-5 (IL-5), IL-6, and IL-13. Transfection of tumor cells with
dominant-negative Stat3 almost completely blocks IL-5 production and
strongly inhibits IL-13 production, whereas IL-6 production is
unaffected. Thus, the data show that malignant CTCL cells themselves might contribute to the change in cytokine pattern accompanying progression of CTCL. In conclusion, constitutively activated Stat3 is
found to mediate a spontaneous IL-5 production and regulate IL-13
production in CTCL cell lines, pointing toward a new role of Stat3 in
malignant transformation.
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