論文 - 詳細
| RRC ID | 62330 |
|---|---|
| 著者 | Higuchi Y, Yasunaga JI, Mitagami Y, Tsukamoto H, Nakashima K, Ohshima K, Matsuoka M. |
| タイトル | HTLV-1 induces T cell malignancy and inflammation by viral antisense factor-mediated modulation of the cytokine signaling. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of a T cell neoplasm and several inflammatory diseases. A viral gene, HTLV-1 bZIP factor (HBZ), induces pathogenic Foxp3-expressing T cells and triggers systemic inflammation and T cell lymphoma in transgenic mice, indicating its significance in HTLV-1-associated diseases. Here we show that, unexpectedly, a proinflammatory cytokine, IL-6, counteracts HBZ-mediated pathogenesis. Loss of IL-6 accelerates inflammation and lymphomagenesis in HBZ transgenic mice. IL-6 innately inhibits regulatory T cell differentiation, suggesting that IL-6 functions as a suppressor against HBZ-associated complications. HBZ up-regulates expression of the immunosuppressive cytokine IL-10. IL-10 promotes T cell proliferation only in the presence of HBZ. As a mechanism of growth promotion by IL-10, HBZ interacts with STAT1 and STAT3 and modulates the IL-10/JAK/STAT signaling pathway. These findings suggest that HTLV-1 promotes the proliferation of infected T cells by hijacking the machinery of regulatory T cell differentiation. IL-10 induced by HBZ likely suppresses the host immune response and concurrently promotes the proliferation of HTLV-1 infected T cells. |
| 巻・号 | 117(24) |
| ページ | 13740-13749 |
| 公開日 | 2020-6-16 |
| DOI | 10.1073/pnas.1922884117 |
| PII | 1922884117 |
| PMID | 32471947 |
| PMC | PMC7306771 |
| MeSH | Animals Basic-Leucine Zipper Transcription Factors / genetics Basic-Leucine Zipper Transcription Factors / immunology* Cell Differentiation Cell Proliferation HTLV-I Infections / genetics HTLV-I Infections / immunology* HTLV-I Infections / pathology HTLV-I Infections / virology Host-Pathogen Interactions Human T-lymphotropic virus 1 / genetics Human T-lymphotropic virus 1 / immunology* Human T-lymphotropic virus 1 / physiology Humans Interleukin-10 / genetics Interleukin-10 / immunology Interleukin-6 / genetics Interleukin-6 / immunology* Lymphoma / genetics Lymphoma / immunology Lymphoma / pathology Lymphoma / virology* Mice Mice, Inbred C57BL Mice, Knockout Retroviridae Proteins / genetics Retroviridae Proteins / immunology* T-Lymphocytes, Regulatory / immunology |
| IF | 9.412 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) 293T(RCB2202) |