Evidence map›Paper›PMID 26037552›Full record

ArticleThe Journal of allergy and clinical immunology2015

Single-cell systems-level analysis of human Toll-like receptor activation defines a chemokine signature in patients with systemic lupus erythematosus.

William E O'Gorman, Elena W Y Hsieh, Erica S Savig, Pier Federico Gherardini, Joseph D Hernandez, Leo Hansmann, Imelda M Balboni, Paul J Utz, Sean C Bendall, Wendy J Fantl and 3 more

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

Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.2field-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

47 citing papers in PubMed, 72 citations in OpenAlex.

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  8. Monocyte regulation by gut microbial signals.Trends in microbiology · 2023
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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

13 authors at 3 institutions in 2 countries.

William E O'GormanDepartment of Microbiology and Immunology, Stanford University, Stanford, Calif.
Elena W Y HsiehDepartment of Microbiology and Immunology, Stanford University, Stanford, Calif; Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, Calif.
Erica S SavigCancer Biology Program, Stanford University, Stanford, Calif.
Pier Federico GherardiniDepartment of Microbiology and Immunology, Stanford University, Stanford, Calif.
Joseph D HernandezDepartment of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, Calif; Department of Pathology, Stanford University, Stanford, Calif.
Leo HansmannDepartment of Microbiology and Immunology, Stanford University, Stanford, Calif.
Imelda M BalboniDepartment of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, Calif.
Paul J UtzDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, Calif.
Sean C BendallDepartment of Pathology, Stanford University, Stanford, Calif.
Wendy J FantlDepartment of Microbiology and Immunology, Stanford University, Stanford, Calif; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford University, Stanford, Calif.
David B LewisDepartment of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, Calif.
Garry P NolanDepartment of Microbiology and Immunology, Stanford University, Stanford, Calif; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, Calif. Electronic address: gnolan@stanford.edu.
Mark M DavisDepartment of Microbiology and Immunology, Stanford University, Stanford, Calif; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, Calif; Howard Hughes Medical Institute, Stanford University, Stanford, Calif. Electronic address: mmdavis@stanford.edu.
Stanford University · USInstitute of Infection and Immunity · CAHoward Hughes Medical Institute · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Systems Biology CoreU19AI100627 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NOLAN, GARRY P · 2012 to 2021
$49.1M
Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
Spectrum Stanford Center for clinical and Translational Research and EducationUL1TR001085 · NCATS · STANFORD UNIVERSITY · PI CULLEN, MARK RICHARD, GREENBERG, HARRY BERNARD · 2013 to 2017
$37.1M
Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
TRIGGERING CELL DEATH IN B CELL LYMPHOMAP01CA034233 · NCI · STANFORD UNIVERSITY · PI LEVY, RONALD · 1985 to 2010
$19.5M
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
Vaccination and infection: indicators of immunological health and responsivenessU19AI090019 · NIAID · STANFORD UNIVERSITY · PI DAVIS, MARK MORRIS · 2010 to 2015
$17.3M
TRANS-NETWORK PROJECTSU54CA143907 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SHIBATA, DARRYL K · 2009 to 2013
$15.2M
MODELING THE ROLE OF PROGRESSION IN FOLLICULAR LYMPHOMAU54CA149145 · NCI · STANFORD UNIVERSITY · PI FELSHER, DEAN W · 2010 to 2014
$12.1M
Software & Hardware Inference Engines for Automated Determination of Primary CellR01CA130826 · NCI · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2008 to 2011
$6.7M
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001085NCI NIH HHS 1R01CA130826NCI NIH HHS 5U54CA1149112NCI NIH HHS 5U54CA143907NCI NIH HHS P01 CA034233NCI NIH HHS R01 CA184968NCI NIH HHS R01CA184968NCI NIH HHS R33 CA183654NCI NIH HHS R33CA183654NCI NIH HHS R33 CA183692NCI NIH HHS R33CA183692NCI NIH HHS T32 CA009302NCI NIH HHS U54 CA149145NCI NIH HHS U54CA149145NHLBI NIH HHS HHSN268201000034CNHLBI NIH HHS N01-HV-00242NIAID NIH HHS 1U19AI100627NIAID NIH HHS 5R01AI073724NIAID NIH HHS HHSN272200700038CNIAID NIH HHS HHSN272201200028CNIAID NIH HHS K08 AI080945NIAID NIH HHS R01 AI073724NIAID NIH HHS R01 AI083757NIAID NIH HHS R01 AI100121NIAID NIH HHS T32 AI007290NIAID NIH HHS T32AI007290NIAID NIH HHS U19 AI057229NIAID NIH HHS U19AI057229NIAID NIH HHS U19 AI090019NIAID NIH HHS U19AI090019NIAID NIH HHS U19 AI100627NIAID NIH HHS U19 AI110491NICHD NIH HHS K12 HD000850NIGMS NIH HHS R00 GM104148NIGMS NIH HHS R00 GM104148-03NIGMS NIH HHS R01GM109836NIGMS NIH HHS T32 GM007276NINDS NIH HHS 1R01NS089533PHS HHS HHSF223201210194C
6 · The paper itself

Abstract

backgroundActivation of Toll-like receptors (TLRs) induces inflammatory responses involved in immunity to pathogens and autoimmune pathogenesis, such as in patients with systemic lupus erythematosus (SLE). Although TLRs are differentially expressed across the immune system, a comprehensive analysis of how multiple immune cell subsets respond in a system-wide manner has not been described.

objectiveWe sought to characterize TLR activation across multiple immune cell subsets and subjects, with the goal of establishing a reference framework against which to compare pathologic processes.

methodsPeripheral whole-blood samples were stimulated with TLR ligands and analyzed by means of mass cytometry simultaneously for surface marker expression, activation states of intracellular signaling proteins, and cytokine production. We developed a novel data visualization tool to provide an integrated view of TLR signaling networks with single-cell resolution. We studied 17 healthy volunteer donors and 8 patients with newly diagnosed and untreated SLE.

resultsOur data revealed the diversity of TLR-induced responses within cell types, with TLR ligand specificity. Subsets of natural killer cells and T cells selectively induced nuclear factor κ light chain enhancer of activated B cells in response to TLR2 ligands. CD14(hi) monocytes exhibited the most polyfunctional cytokine expression patterns, with more than 80 distinct cytokine combinations. Monocytic TLR-induced cytokine patterns were shared among a group of healthy donors, with minimal intraindividual and interindividual variability. Furthermore, autoimmune disease altered baseline cytokine production; newly diagnosed untreated SLE patients shared a distinct monocytic chemokine signature, despite clinical heterogeneity.

conclusionMass cytometry defined a systems-level reference framework for human TLR activation, which can be applied to study perturbations in patients with inflammatory diseases, such as SLE.

Indexed as

Cells, CulturedChemokinesHumansKiller Cells, NaturalLipopolysaccharide ReceptorsLupus Erythematosus, SystemicLymphocyte ActivationMonocytesNF-kappa BOrgan SpecificitySignal TransductionSingle-Cell AnalysisT-LymphocytesToll-Like ReceptorsTranscriptomeChemokinesLipopolysaccharide ReceptorsNF-kappa BToll-Like ReceptorsinflammationMass cytometrymonocyte chemotactic protein 1monocytessystemic lupus erythematosusToll-like receptors

Identifiers

PMID26037552
PMCPMC4640970
OpenAlexW2156717635

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Registered trials

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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.