Evidence map›Paper›PMID 25917086›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2015

The Processed Amino-Terminal Fragment of Human TLR7 Acts as a Chaperone To Direct Human TLR7 into Endosomes.

Madeleine M Hipp, Dawn Shepherd, Sarah Booth, Dominic Waithe, Caetano Reis e Sousa, Vincenzo Cerundolo

Open access · hybridAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. 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

6 authors at 4 institutions in 1 country.

Madeleine M HippMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom; and vincenzo.cerundolo@imm.ox.ac.uk madeleine.hipp@curevac.com.
Dawn ShepherdMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom; and.
Sarah BoothMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom; and.
Dominic WaitheMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom; and.
Caetano Reis e SousaThe Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, United Kingdom.
Vincenzo CerundoloMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom; and vincenzo.cerundolo@imm.ox.ac.uk madeleine.hipp@curevac.com.
MRC Weatherall Institute of Molecular Medicine · GBUniversity of Oxford · GBMRC Human Immunology Unit · GBThe Honourable Society of Lincoln's Inn · GB

Funding

Cancer Research UK 15689Cancer Research UK 17722Cancer Research UK A11331Cancer Research UK C399/A2291Medical Research Council G1000800Medical Research Council MC_UU_12010/1Medical Research Council MR/K01577X/1Wellcome Trust 084923
6 · The paper itself

Abstract

TLR7 mediates innate immune responses to viral RNA in endocytic compartments. Mouse and human (h)TLR7 undergo proteolytic cleavage, resulting in the generation of a C-terminal fragment that accumulates in endosomes and associates with the signaling adaptor MyD88 upon receptor triggering by TLR7 agonists. Although mouse TLR7 is cleaved in endosomes by acidic proteases, hTLR7 processing can occur at neutral pH throughout the secretory pathway through the activity of furin-like proprotein convertases. However, the mechanisms by which cleaved hTLR7 reaches the endosomal compartment remain unclear. In this study, we demonstrate that, after hTLR7 proteolytic processing, the liberated amino (N)-terminal fragment remains bound to the C terminus through disulfide bonds and provides key trafficking information that ensures correct delivery of the complex to endosomal compartments. In the absence of the N-terminal fragment, the C-terminal fragment is redirected to the cell surface, where it is functionally inactive. Our data reveal a novel role for the N terminus of hTLR7 as a molecular chaperone that provides processed hTLR7 with the correct targeting instructions to reach the endosomal compartment, hence ensuring its biological activity and preventing inadvertent cell surface responses to self-RNA.

Indexed as

Carrier ProteinsCell LineEndosomesHEK293 CellsHumansInterleukin-8Molecular ChaperonesMyeloid Differentiation Factor 88Peptide FragmentsProprotein ConvertasesProtein Processing, Post-TranslationalProtein TransportProteolysisToll-Like Receptor 4Toll-Like Receptor 7Carrier ProteinsCXCL8 protein, humanInterleukin-8Molecular ChaperonesMYD88 protein, humanMyeloid Differentiation Factor 88Peptide FragmentsProprotein ConvertasesTLR4 protein, humanTLR7 protein, humanToll-Like Receptor 4Toll-Like Receptor 7

Identifiers

PMID25917086
PMCPMC4432728
OpenAlexW1763281604

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.