| Title: | Constitutive aryl hydrocarbon receptor signaling constrains type I interferon–mediated antiviral innate defense |
| Authors: | Yamada, Taisho Browse this author |
| Horimoto, Hiromasa Browse this author |
| Kameyama, Takeshi Browse this author →KAKEN DB |
| Hayakawa, Sumio Browse this author |
| Yamato, Hiroaki Browse this author |
| Dazai, Masayoshi Browse this author |
| Takada, Ayato Browse this author →KAKEN DB |
| Kida, Hiroshi Browse this author →KAKEN DB |
| Bott, Debbie Browse this author |
| Zhou, Angela C Browse this author |
| Hutin, David Browse this author |
| Watts, Tania H Browse this author |
| Asaka, Masahiro Browse this author →KAKEN DB |
| Matthews, Jason Browse this author |
| Takaoka, Akinori Browse this author →KAKEN DB |
| Issue Date: | Jun-2016 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Nature Immunology |
| Volume: | 17 |
| Issue: | 6 |
| Start Page: | 687 |
| End Page: | 694 |
| Publisher DOI: | 10.1038/ni.3422 |
| PMID: | 27089381 |
| 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. |
| Description: | Supplementary materials are available on the publisher's website. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/63086 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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