Evidence map›Paper›PMID 26683155›Full record

ReviewImmunological reviews2016

Negative regulation of TLR signaling in myeloid cells--implications for autoimmune diseases.

Jessica A Hamerman, Jessica Pottle, Minjian Ni, Yantao He, Zhong-Yin Zhang, Jane H Buckner

Abstract readReview
In one paragraph

Review in Immunological reviews, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 5% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Antioxidants (Basel, Switzerland) · 2026
    Article
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  16. Clinical and experimental treatment of type 1 diabetes.Clinical and experimental immunology · 2022
    Review
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  20. Article

1 more citing papers are in PubMed but not listed here.

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

6 authors at 3 institutions in 1 country.

Jessica A HamermanImmunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Jessica PottleImmunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Minjian NiImmunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Yantao HeDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Zhong-Yin ZhangDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Jane H BucknerTranslational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Benaroya Research InstituteIndiana University – Purdue University Indianapolis · USVirginia Mason Medical Center · US

Funding

Virginia Mason/UCHSC Autoimmune Prevention CenterU19AI050864 · NIAID · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2001 to 2011
$29.2M
Structure/Function of Protein Tyrosine PhosphatasesR01CA069202 · NCI · YESHIVA UNIVERSITY · PI Zhong-Yin Zhang · 1996 to 2026
$7.3M
Regulation of dendritic cell inflammatory responsesR01AI081948 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI HAMERMAN, JESSICA A · 2010 to 2014
$2.2M
BCAP/PI3K regulation of innate immunity to Listeria monocytogenesR01AI113325 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI HAMERMAN, JESSICA A · 2015 to 2019
$2.0M
Impact of the autoimmunity associated PTPN22 1858TR01AI083455 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI BUCKNER, JANE HOYT · 2011 to 2014
$1.7M
NCI NIH HHS R01 CA069202NCI NIH HHS R01CA69202NIAID NIH HHS R01 AI081948NIAID NIH HHS R01AI081948NIAID NIH HHS R01 AI083455NIAID NIH HHS R01AI083455NIAID NIH HHS R01 AI113325NIAID NIH HHS R01AI113325NIAID NIH HHS U19 AI050864NIAID NIH HHS U19AI050864
6 · The paper itself

Abstract

Toll-like receptors (TLR) are transmembrane pattern recognition receptors that recognize microbial ligands and signal for production of inflammatory cytokines and type I interferon in macrophages and dendritic cells (DC). Whereas TLR-induced inflammatory mediators are required for pathogen clearance, many are toxic to the host and can cause pathological inflammation when over-produced. This is demonstrated by the role of TLR-induced cytokines in autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. Because of the potent effects of TLR-induced cytokines, we have diverse mechanisms to dampen TLR signaling. Here, we highlight three pathways that participate in inhibition of TLR responses in macrophages and DC, and their implications in autoimmunity; A20, encoded by the TNFAIP3 gene, Lyp encoded by the PTPN22 gene, and the BCAP/PI3K pathway. We present new findings that Lyp promotes TLR responses in primary human monocytes and that the autoimmunity risk Lyp620W variant is more effective at promoting TLR-induced interleukin-6 than the non-risk Lyp620R protein. This suggests that Lyp serves to downregulate a TLR inhibitory pathway in monocytes, and we propose that Lyp inhibits the TREM2/DAP12 inhibitory pathway. Overall, these pathways demonstrate distinct mechanisms of negative regulation of TLR responses, and all impact autoimmune disease pathogenesis and treatment.

Indexed as

AnimalsAutoimmune DiseasesCarrier ProteinsDendritic CellsDNA-Binding ProteinsHumansImmunomodulationIntracellular Signaling Peptides and ProteinsMacrophagesMyeloid CellsNuclear ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 22Signal TransductionToll-Like ReceptorsTumor Necrosis Factor alpha-Induced Protein 3Carrier ProteinsDNA-Binding ProteinsIntracellular Signaling Peptides and ProteinsNuclear ProteinsODF2L protein, humanProtein Tyrosine Phosphatase, Non-Receptor Type 22PTPN22 protein, humanTNFAIP3 protein, humanToll-Like ReceptorsTumor Necrosis Factor alpha-Induced Protein 3autoimmune diseasedendritic cellsmacrophagessignal transductionToll-like receptors

Identifiers

PMID26683155
PMCPMC4703580
OpenAlexW2221307589

What OpenQuestion holds

Textmetadata
LicenceTDM
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.