HTLV-1 bZIP factor induces inflammation through labile Foxp3 expression.

Bibliographic Details
Title: HTLV-1 bZIP factor induces inflammation through labile Foxp3 expression.
Authors: Nanae Yamamoto-Taguchi, Yorifumi Satou, Paola Miyazato, Koichi Ohshima, Masanori Nakagawa, Koko Katagiri, Tatsuo Kinashi, Masao Matsuoka
Source: PLoS Pathogens, Vol 9, Iss 9, p e1003630 (2013)
Publisher Information: Public Library of Science (PLoS), 2013.
Publication Year: 2013
Collection: LCC:Immunologic diseases. Allergy
LCC:Biology (General)
Subject Terms: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
More Details: Human T-cell leukemia virus type 1 (HTLV-1) causes both a neoplastic disease and inflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 basic leucine zipper factor (HBZ) gene is encoded in the minus strand of the proviral DNA and is constitutively expressed in infected cells and ATL cells. HBZ increases the number of regulatory T (Treg) cells by inducing the Foxp3 gene transcription. Recent studies have revealed that some CD4⁺Foxp3⁺ T cells are not terminally differentiated but have a plasticity to convert to other T-cell subsets. Induced Treg (iTreg) cells tend to lose Foxp3 expression, and may acquire an effector phenotype accompanied by the production of inflammatory cytokines, such as interferon-γ (IFN-γ). In this study, we analyzed a pathogenic mechanism of chronic inflammation related with HTLV-1 infection via focusing on HBZ and Foxp3. Infiltration of lymphocytes was observed in the skin, lung and intestine of HBZ-Tg mice. As mechanisms, adhesion and migration of HBZ-expressing CD4⁺ T cells were enhanced in these mice. Foxp3⁻CD4⁺ T cells produced higher amounts of IFN-γ compared to those from non-Tg mice. Expression of Helios was reduced in Treg cells from HBZ-Tg mice and HAM/TSP patients, indicating that iTreg cells are predominant. Consistent with this finding, the conserved non-coding sequence 2 region of the Foxp3 gene was hypermethylated in Treg cells of HBZ-Tg mice, which is a characteristic of iTreg cells. Furthermore, Treg cells in the spleen of HBZ-transgenic mice tended to lose Foxp3 expression and produced an excessive amount of IFN-γ, while Foxp3 expression was stable in natural Treg cells of the thymus. HBZ enhances the generation of iTreg cells, which likely convert to Foxp3⁻T cells producing IFN-γ. The HBZ-mediated proinflammatory phenotype of CD4⁺ T cells is implicated in the pathogenesis of HTLV-1-associated inflammation.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1553-7366
1553-7374
Relation: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24068936/?tool=EBI; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374
DOI: 10.1371/journal.ppat.1003630
Access URL: https://doaj.org/article/a0ddf3d0cda04233a17f02adaa4eba66
Accession Number: edsdoj.0ddf3d0cda04233a17f02adaa4eba66
Database: Directory of Open Access Journals
More Details
ISSN:15537366
15537374
DOI:10.1371/journal.ppat.1003630
Published in:PLoS Pathogens
Language:English