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HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo

Satou, Y; Yasunaga, J; Zhao, T; Yoshida, M; Miyazato, P; Takai, K; Shimizu, K; ... Matsuoka, M; + view all (2010) HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo. PLoS Pathogens , 7 (2) , Article e1001274. 10.1371/journal.ppat.1001274. Green open access

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Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the causal agent of a neoplastic disease of CD4+ T cells, adult T-cell leukemia (ATL), and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, and inflammatory lung diseases. ATL cells, which constitutively express CD25, resemble CD25+CD4+ regulatory T cells (T(reg)). Approximately 60% of ATL cases indeed harbor leukemic cells that express FoxP3, a key transcription factor for T(reg) cells. HTLV-1 encodes an antisense transcript, HTLV-1 bZIP factor (HBZ), which is expressed in all ATL cases. In this study, we show that transgenic expression of HBZ in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice, resembling diseases observed in HTLV-1 infected individuals. In HBZ-transgenic mice, CD4+Foxp3+ T(reg) cells and effector/memory CD4+ T cells increased in vivo. As a mechanism of increased T(reg) cells, HBZ expression directly induced Foxp3 gene transcription in T cells. The increased CD4+Foxp3+ T(reg) cells in HBZ transgenic mice were functionally impaired while their proliferation was enhanced. HBZ could physically interact with Foxp3 and NFAT, thereby impairing the suppressive function of T(reg) cells. Thus, the expression of HBZ in CD4+ T cells is a key mechanism of HTLV-1-induced neoplastic and inflammatory diseases.

Type: Article
Title: HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.ppat.1001274
Publisher version: http://dx.doi.org/10.1371/journal.ppat.1001274
Language: English
Additional information: © 2011 Satou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1332869
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