論文 - 詳細
| RRC ID | 34731 |
|---|---|
| 著者 | Araya N, Sato T, Ando H, Tomaru U, Yoshida M, Coler-Reilly A, Yagishita N, Yamauchi J, Hasegawa A, Kannagi M, Hasegawa Y, Takahashi K, Kunitomo Y, Tanaka Y, Nakajima T, Nishioka K, Utsunomiya A, Jacobson S, Yamano Y. |
| タイトル | HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells. |
| ジャーナル | J Clin Invest |
| Abstract |
Human T-lymphotropic virus type 1 (HTLV-1) is linked to multiple diseases, including the neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia/lymphoma. Evidence suggests that HTLV-1, via the viral protein Tax, exploits CD4+ T cell plasticity and induces transcriptional changes in infected T cells that cause suppressive CD4+CD25+CCR4+ Tregs to lose expression of the transcription factor FOXP3 and produce IFN-γ, thus promoting inflammation. We hypothesized that transformation of HTLV-1-infected CCR4+ T cells into Th1-like cells plays a key role in the pathogenesis of HAM/TSP. Here, using patient cells and cell lines, we demonstrated that Tax, in cooperation with specificity protein 1 (Sp1), boosts expression of the Th1 master regulator T box transcription factor (T-bet) and consequently promotes production of IFN-γ. Evaluation of CSF and spinal cord lesions of HAM/TSP patients revealed the presence of abundant CD4+CCR4+ T cells that coexpressed the Th1 marker CXCR3 and produced T-bet and IFN-γ. Finally, treatment of isolated PBMCs and CNS cells from HAM/TSP patients with an antibody that targets CCR4+ T cells and induces cytotoxicity in these cells reduced both viral load and IFN-γ production, which suggests that targeting CCR4+ T cells may be a viable treatment option for HAM/TSP. |
| 巻・号 | 124(8) |
| ページ | 3431-42 |
| 公開日 | 2014-8-1 |
| DOI | 10.1172/JCI75250 |
| PII | 75250 |
| PMID | 24960164 |
| PMC | PMC4109535 |
| MeSH | Adult Aged Antibodies, Monoclonal / therapeutic use CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / virology* Cell Line Cytotoxicity, Immunologic Female Gene Products, tax / immunology Human T-lymphotropic virus 1 / immunology* Human T-lymphotropic virus 1 / pathogenicity* Humans Immunotherapy Interferon-gamma / biosynthesis Interferon-gamma / genetics Male Middle Aged Paraparesis, Tropical Spastic / genetics Paraparesis, Tropical Spastic / immunology Paraparesis, Tropical Spastic / virology Receptors, CCR4 / antagonists & inhibitors Receptors, CCR4 / immunology Receptors, CCR4 / metabolism* Sp1 Transcription Factor / immunology T-Box Domain Proteins / genetics T-Box Domain Proteins / immunology T-Lymphocytes, Regulatory / immunology T-Lymphocytes, Regulatory / virology Th1 Cells / immunology* Th1 Cells / virology* Viral Load / immunology |
| IF | 11.864 |
| 引用数 | 50 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-MCS (RDB04377) |