Evidence map›Paper›PMID 39126651›Full record

ArticleCell reports2024

Defective endomembrane dynamics in Rab27a deficiency impairs nucleic acid sensing and cytokine secretion in immune cells.

Juan Yu, Elsa Meneses-Salas, Jennifer L Johnson, Susanna Manenti, Mouad Ait Kbaich, Danni Chen, Kasra Askari, Jing He, Aparna Shukla, Binchu Shaji and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

20 authors.

Juan YuDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Elsa Meneses-SalasDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jennifer L JohnsonDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Susanna ManentiDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Mouad Ait KbaichDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Danni ChenDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kasra AskariDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jing HeDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Aparna ShuklaDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Binchu ShajiDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Rosana Gonzalez-QuintialDepartment of Autoimmunity & Viral Immunopathology, San Diego BioMed Institute, San Diego, CA 92121, USA.
Ben A CrokerDepartment of Pediatrics, University of California San Diego; La Jolla, CA 92093, USA.
Jinzhong ZhangDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hal HoffmanDepartment of Pediatrics, University of California San Diego; La Jolla, CA 92093, USA.
William B KiossesDivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Catherine HedrickDepartment of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Kersi PestonjamaspDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Nathan WineingerScripps Research Translational Institute, The Scripps Research Institute, La Jolla, CA 92037, USA.
Roberto BaccalaDepartment of Autoimmunity & Viral Immunopathology, San Diego BioMed Institute, San Diego, CA 92121, USA.
Sergio D CatzDepartment of Molecular and Cellular Biology, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: scatz@scripps.edu.

Funding

Neutrophil Survival and Demise During Inflammatory StatesP01HL152958 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI CATZ, SERGIO DANIEL · 2021 to 2025
$12.4M
Vesicular trafficking mechanisms regulating granulocyte functionR01HL088256 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI Sergio Daniel Catz · 2009 to 2026
$9.0M
Molecular and Cellular Mechanisms of the Lysosomal Storage Disease CystinosisR01DK110162 · NIDDK · SCRIPPS RESEARCH INSTITUTE, THE · PI CATZ, SERGIO DANIEL, CHERQUI, STEPHANIE · 2017 to 2025
$4.7M
Synergistic effects of silica exposure, virus infection and genetic predisposition in systemic autoimmunityR01ES031082 · NIEHS · SCRIPPS RESEARCH INSTITUTE, THE · PI BACCALA, ROBERTO G · 2020 to 2024
$2.5M
Small Molecule inhibitors of late endosomal pro-inflammatory signalingR01AR070837 · NIAMS · SCRIPPS RESEARCH INSTITUTE, THE · PI CATZ, SERGIO DANIEL, ROSEN, HUGH · 2017 to 2019
$1.3M
Differential role of TASL and SLC15A4 in TLR responses to nucleic acids and lupus developmentR21AI174237 · NIAID · SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE · PI BACCALA, ROBERTO G · 2023 to 2024
$528k
NHLBI NIH HHS P01 HL152958NHLBI NIH HHS R01 HL088256NIAID NIH HHS R21 AI174237NIAMS NIH HHS R01 AR070837NIDDK NIH HHS R01 DK110162NIEHS NIH HHS R01 ES031082
6 · The paper itself

Abstract

Endosomal Toll-like receptors (eTLRs) are essential for the sensing of non-self through RNA and DNA detection. Here, using spatiotemporal analysis of vesicular dynamics, super-resolution microscopy studies, and functional assays, we show that endomembrane defects associated with the deficiency of the small GTPase Rab27a cause delayed eTLR ligand recognition, defective early signaling, and impaired cytokine secretion. Rab27a-deficient neutrophils show retention of eTLRs in amphisomes and impaired ligand internalization. Extracellular signal-regulated kinase (ERK) signaling and β2-integrin upregulation, early responses to TLR7 and TLR9 ligands, are defective in Rab27a deficiency. CpG-stimulated Rab27a-deficient neutrophils present increased tumor necrosis factor alpha (TNF-α) secretion and decreased secretion of a selected group of mediators, including interleukin (IL)-10. In vivo, CpG-challenged Rab27a-null mice show decreased production of type I interferons (IFNs) and IFN-γ, and the IFN-α secretion defect is confirmed in Rab27a-null plasmacytoid dendritic cells. Our findings have significant implications for immunodeficiency, inflammation, and CpG adjuvant vaccination.

Indexed as

Cytokinesrab27 GTP-Binding ProteinsToll-Like Receptor 9AnimalsEndosomesInterferon-gammaMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutNeutrophilsNucleic Acidsrab GTP-Binding ProteinsSignal TransductionToll-Like Receptor 7Tumor Necrosis Factor-alphaCytokinesInterferon-gammaMembrane GlycoproteinsNucleic AcidsRab27a protein, mouserab27 GTP-Binding Proteinsrab GTP-Binding ProteinsTlr7 protein, mouseTlr9 protein, mouseToll-Like Receptor 7Toll-Like Receptor 9Tumor Necrosis Factor-alphaamphisomeCP: Cell biologyCpGCP: Immunologyendosomal Toll-like receptorIFN-αIL-10neutrophilplasmacytoid Dendritic CellRab GTPaseTLR7TLR9

Identifiers

PMID39126651
PMCPMC13078896

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.