Evidence map›Paper›PMID 25135299›Full record

ArticleThe Journal of experimental medicine2014

Classical Flt3L-dependent dendritic cells control immunity to protein vaccine.

Niroshana Anandasabapathy, Rachel Feder, Shamim Mollah, Sze-Wah Tse, Maria Paula Longhi, Saurabh Mehandru, Ines Matos, Cheolho Cheong, Darren Ruane, Lucas Brane and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

64 citing papers in PubMed, 93 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 2 countries.

Niroshana AnandasabapathyLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Department of Dermatology/Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, MA 02115 nanandasabapathy@partners.org.
Rachel FederLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Shamim MollahLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Sze-Wah TseDepartment of Dermatology/Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, MA 02115.
Maria Paula LonghiLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Saurabh MehandruLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Ines MatosLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Cheolho CheongLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Darren RuaneLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Lucas BraneLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Angela TeixeiraLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Joseph DobrinLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Olga MizeninaLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Chae Gyu ParkLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Matthew MeredithLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Björn E ClausenInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, D-55131 Mainz, Germany.
Michel C NussenzweigLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Ralph M SteinmanLaboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
Rockefeller University · USBrigham and Women's Hospital · USJohannes Gutenberg University Mainz · DE

Funding

Protein Expression CoreP01AI081677 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 2009 to 2013
$10.6M
Properties of Mouse of Dendritic Cells and MacrophagesR01AI013013 · NIAID · ROCKEFELLER UNIVERSITY · PI MOJSOV, SVETLANA · 1985 to 2015
$8.9M
Dendritic Cells and the Pathogenesis of HIV-1 InfectionR37AI040045 · NIAID · ROCKEFELLER UNIVERSITY · PI STEINMAN, RALPH MARVIN · 2001 to 2010
$6.1M
Transforming Translational Science and Education to Benefit Human HealthKL2RR024142 · NCRR · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2006 to 2011
$4.5M
Transforming Translational Science and Education to Benefit Human HealthKL2TR000151 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$2.1M
The clinical use of Flt3L - an immune adjuvant to potentiate Dendritic CellsK23AR063461 · NIAMS · ROCKEFELLER UNIVERSITY · PI ANANDASABAPATHY, NIROSHANA · 2012 to 2016
$726k
Identification and vaccine adjuvant responses of dendritic cells in humansR56AI040045 · NIAID · ROCKEFELLER UNIVERSITY · PI SCHLESINGER, SARAH JANE · 2011 to 2011
$520k
DENDRITIC CELLS AND THE PATHOGENESIS OF HIV-1 INFECTIONR01AI040045 · NIAID · ROCKEFELLER UNIVERSITY · PI STEINMAN, RALPH M. · 1996 to 2000
$457k
British Heart Foundation FS/13/49/30421NCATS NIH HHS KL2 TR000151NCRR NIH HHS KL2 RR024142NCRR NIH HHS RR024142NIAID NIH HHS AI40045NIAID NIH HHS N01 AI040045NIAID NIH HHS P01 AI081677NIAID NIH HHS R01 AI013013NIAID NIH HHS R01 AI040045NIAMS NIH HHS AR063461-01A1NIAMS NIH HHS K23 AR063461PHS HHS 13013PHS HHS 81677
6 · The paper itself

Abstract

DCs are critical for initiating immunity. The current paradigm in vaccine biology is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs (cDCs) cooperate in the draining LNs to initiate priming and proliferation of T cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3 ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3 deletion reduces T cell responses by 50%. Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find immunity is controlled by cDCs and actively tempered in vivo by migDCs. Deletion of Langerin(+) DC or blockade of DC migration improves immunity. Consistent with an immune-regulatory role, transcriptomic analyses reveals different skin migDC subsets in both mouse and human cluster together, and share immune-suppressing gene expression and regulatory pathways. These data reveal that protective immunity to protein vaccines is controlled by Flt3L-dependent, LN-resident cDCs.

Indexed as

AnimalsAntigen PresentationAntigens, SurfaceDendritic CellsFemaleGene ExpressionHumansImmunity, HumoralInjections, IntradermalInjections, SubcutaneousInterferon-gammaLectins, C-TypeLigandsMaleMannose-Binding LectinsMembrane ProteinsAntigens, SurfaceCd207 protein, mouseflt3 ligand proteinInterferon-gammaLectins, C-TypeLigandsMannose-Binding LectinsMembrane ProteinsOvalbuminProteinsTranscription FactorsVaccinesZbtb46 protein, mouse

Identifiers

PMID25135299
PMCPMC4144735
OpenAlexW2031537098

What OpenQuestion holds

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Read underepoch 390

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.