ID | 63445 |
フルテキストURL | |
著者 |
Matsumoto, Yoshinori
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
researchmap
Dimitriou, Ioannis D.
Princess Margaret Cancer Centre, University Health Network, University of Toronto
La Rose, Jose
Princess Margaret Cancer Centre, University Health Network, University of Toronto
Lim, Melissa
Princess Margaret Cancer Centre, University Health Network, University of Toronto
Camilleri, Susan
Centre for Modeling Human Disease, Toronto Centre for Phenogenomics
Law, Napoleon
Centre for Modeling Human Disease, Toronto Centre for Phenogenomics
Adissu, Hibret A.
Labcorp Early Development Laboratories Inc.
Tong, Jiefei
Program in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics
Moran, Michael F.
Program in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics
Chruscinski, Andrzej
Multi-Organ Transplant Program, University Health Network
He, Fang
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Asano, Yosuke
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Katsuyama, Takayuki
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sada, Ken-ei
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
researchmap
Wada, Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
Rottapel, Robert
Princess Margaret Cancer Centre, University Health Network, University of Toronto
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抄録 | Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response.
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発行日 | 2022-4-1
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出版物タイトル |
Journal of Clinical Investigation
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巻 | 132巻
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号 | 7号
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出版者 | American Society for Clinical Investigation
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開始ページ | e140869
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ISSN | 1558-8238
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2022, Matsumoto et al.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1172/jci140869
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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Citation | Citation Information: J Clin Invest. 2022;132(7):e140869. https://doi.org/10.1172/JCI140869.
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助成機関名 |
Japan Society for the Promotion of Science
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助成番号 | JP21H02429
JP19H03447
JP21J10565
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