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

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 constituti...

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Autores principales:	Yorifumi Satou, Jun-Ichirou Yasunaga, Tiejun Zhao, Mika Yoshida, Paola Miyazato, Ken Takai, Kei Shimizu, Koichi Ohshima, Patrick L Green, Naganari Ohkura, Tomoyuki Yamaguchi, Masahiro Ono, Shimon Sakaguchi, Masao Matsuoka
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cc14f0a6e9634ff29104d1d7e8a46750
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spelling	oai:doaj.org-article:cc14f0a6e9634ff29104d1d7e8a467502021-11-18T06:03:37ZHTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.1553-73661553-737410.1371/journal.ppat.1001274https://doaj.org/article/cc14f0a6e9634ff29104d1d7e8a467502011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347344/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Human 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.Yorifumi SatouJun-Ichirou YasunagaTiejun ZhaoMika YoshidaPaola MiyazatoKen TakaiKei ShimizuKoichi OhshimaPatrick L GreenNaganari OhkuraTomoyuki YamaguchiMasahiro OnoShimon SakaguchiMasao MatsuokaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 2, p e1001274 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Yorifumi Satou Jun-Ichirou Yasunaga Tiejun Zhao Mika Yoshida Paola Miyazato Ken Takai Kei Shimizu Koichi Ohshima Patrick L Green Naganari Ohkura Tomoyuki Yamaguchi Masahiro Ono Shimon Sakaguchi Masao Matsuoka HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.
description	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.
format	article
author	Yorifumi Satou Jun-Ichirou Yasunaga Tiejun Zhao Mika Yoshida Paola Miyazato Ken Takai Kei Shimizu Koichi Ohshima Patrick L Green Naganari Ohkura Tomoyuki Yamaguchi Masahiro Ono Shimon Sakaguchi Masao Matsuoka
author_facet	Yorifumi Satou Jun-Ichirou Yasunaga Tiejun Zhao Mika Yoshida Paola Miyazato Ken Takai Kei Shimizu Koichi Ohshima Patrick L Green Naganari Ohkura Tomoyuki Yamaguchi Masahiro Ono Shimon Sakaguchi Masao Matsuoka
author_sort	Yorifumi Satou
title	HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.
title_short	HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.
title_full	HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.
title_fullStr	HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.
title_full_unstemmed	HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.
title_sort	htlv-1 bzip factor induces t-cell lymphoma and systemic inflammation in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/cc14f0a6e9634ff29104d1d7e8a46750
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HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.

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