論文 - 詳細
| RRC ID | 46996 |
|---|---|
| 著者 | Yamada T, Horimoto H, Kameyama T, Hayakawa S, Yamato H, Dazai M, Takada A, Kida H, Bott D, Zhou AC, Hutin D, Watts TH, Asaka M, Matthews J, Takaoka A. |
| タイトル | Constitutive aryl hydrocarbon receptor signaling constrains type I interferon-mediated antiviral innate defense. |
| ジャーナル | Nat Immunol |
| Abstract |
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxic activity of many environmental xenobiotics. However, its role in innate immune responses during viral infection is not fully understood. Here we demonstrate that constitutive AHR signaling negatively regulates the type I interferon (IFN-I) response during infection with various types of virus. Virus-induced IFN-β production was enhanced in AHR-deficient cells and mice and resulted in restricted viral replication. We found that AHR upregulates expression of the ADP-ribosylase TIPARP, which in turn causes downregulation of the IFN-I response. Mechanistically, TIPARP interacted with the kinase TBK1 and suppressed its activity by ADP-ribosylation. Thus, this study reveals the physiological importance of endogenous activation of AHR signaling in shaping the IFN-I-mediated innate response and, further, suggests that the AHR-TIPARP axis is a potential therapeutic target for enhancing antiviral responses. |
| 巻・号 | 17(6) |
| ページ | 687-94 |
| 公開日 | 2016-6-1 |
| DOI | 10.1038/ni.3422 |
| PII | ni.3422 |
| PMID | 27089381 |
| MeSH | Animals Gene Expression Regulation HEK293 Cells HeLa Cells Humans Immunity, Innate Interferon Type I / metabolism Mice Mice, Inbred C57BL Mice, Knockout Poly(ADP-ribose) Polymerases / genetics Poly(ADP-ribose) Polymerases / metabolism* RNA, Small Interfering / genetics Receptors, Aryl Hydrocarbon / genetics Receptors, Aryl Hydrocarbon / metabolism* Signal Transduction Transcriptional Activation Virus Diseases / immunology* Virus Replication |
| IF | 20.479 |
| 引用数 | 55 |
| WOS 分野 | IMMUNOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 57 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 遺伝子材料 | pIRM21-3HA-hTIPARP(WT) (RDB14323) pIRM21-3HA-N-hTIPARP (RDB14324) pIRM21-3HA-C-hTIPARP (RDB14325) pCAG-YFP-hTIPARP (RDB14326) pFastBac1-GST-hTIPARP(WT) (RDB14327) pFastBac1-GST-hTIPARP(H532A) (RDB14328) pCXN2-FLAG-hMAVS (RDB14329) pCXN2-FLAG-hTBK1(WT) (RDB14330) pCXN2-FLAG-hTBK1(KD) (RDB14331) pCXN2-FLAG-hTBK1(ULD+CC) (RDB14332). |