Evidence map›Paper›PMID 35362478›Full record

ArticleThe Journal of clinical investigation2022

Tankyrase represses autoinflammation through the attenuation of TLR2 signaling.

Yoshinori Matsumoto, Ioannis D Dimitriou, Jose La Rose, Melissa Lim, Susan Camilleri, Napoleon Law, Hibret A Adissu, Jiefei Tong, Michael F Moran, Andrzej Chruscinski and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 5 countries.

Yoshinori MatsumotoPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Ioannis D DimitriouPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Jose La RosePrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Melissa LimPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Susan CamilleriCentre for Modeling Human Disease, Toronto Centre for Phenogenomics, Toronto, Ontario, Canada.
Napoleon LawCentre for Modeling Human Disease, Toronto Centre for Phenogenomics, Toronto, Ontario, Canada.
Hibret A AdissuLabcorp Early Development Laboratories Inc., Chantilly, Virginia, USA.
Jiefei TongProgram in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics.
Michael F MoranProgram in Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics.
Andrzej ChruscinskiMulti-Organ Transplant Program, University Health Network.
Fang HeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yosuke AsanoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Takayuki KatsuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Ken-Ei SadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Jun WadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Robert RottapelPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Okayama University · JPUniversity Health Network · CAGreat Ormond Street Hospital · GBToronto Centre for Phenogenomics · CALabCorp (United States) · USSt. Michael's Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Autoimmune DiseasesInflammationTankyrasesToll-Like Receptor 2Adaptor Proteins, Signal TransducingAnimalsMiceSignal TransductionSyk KinaseAdaptor Proteins, Signal TransducingSyk KinaseTankyrasesTlr2 protein, mouseTnks protein, mouseToll-Like Receptor 2AutoimmunityCytokinesInflammation

Identifiers

PMID35362478
PMCPMC8970677
OpenAlexW4220994403

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.