Evidence map›Paper›PMID 32471881›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2020

Triggering of the cGAS-STING Pathway in Human Plasmacytoid Dendritic Cells Inhibits TLR9-Mediated IFN Production.

Pratik Deb, Jihong Dai, Sukhwinder Singh, Evelyne Kalyoussef, Patricia Fitzgerald-Bocarsly

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

56 citing papers in PubMed, 63 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Pratik DebRutgers School of Graduate Studies, Newark, NJ 07103.ORCID 0000-0001-6680-7913
Jihong DaiDepartment of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103.
Sukhwinder SinghDepartment of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103.
Evelyne KalyoussefDepartment of Otolaryngology, Rutgers New Jersey Medical School, Newark, NJ 07103.ORCID 0000-0002-1016-0070
Patricia Fitzgerald-BocarslyRutgers School of Graduate Studies, Newark, NJ 07103; bocarsly@njms.rutgers.edu.ORCID 0000-0002-7604-3184
Rutgers, The State University of New Jersey · US

Funding

ROLE OF INTERFERON-ALPHA IN AIDS PATHOGENESISR01AI026806 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI FITZGERALD-BOCARSLY, PATRICIA · 1991 to 2014
$6.0M
Contribution of plasmacytoid DCs to immune senescence in HIV infectionR01AI106125 · NIAID · RBHS-NEW JERSEY MEDICAL SCHOOL · PI FITZGERALD-BOCARSLY, PATRICIA · 2014 to 2017
$1.6M
ImageStream X Mark II for NJMS Flow CoreS10OD018103 · OD · RBHS-NEW JERSEY MEDICAL SCHOOL · PI FITZGERALD-BOCARSLY, PATRICIA · 2014 to 2014
$440k
NIAID NIH HHS R01 AI026806NIAID NIH HHS R01 AI106125NIH HHS S10 OD018103
6 · The paper itself

Abstract

Plasmacytoid dendritic cells (pDCs) are potent producers of type I and type III IFNs and play a major role in antiviral immunity and autoimmune disorders. The innate sensing of nucleic acids remains the major initiating factor for IFN production by pDCs. TLR-mediated sensing of nucleic acids via endosomal pathways has been studied and documented in detail, whereas the sensing of DNA in cytosolic compartment in human pDCs remains relatively unexplored. We now demonstrate the existence and functionality of the components of cytosolic DNA-sensing pathway comprising cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of IFN gene (STING) in human pDCs. cGAS was initially located in the cytosolic compartment of pDCs and time-dependently colocalized with non-CpG double-stranded immunostimulatory DNA (ISD). Following the colocalization of ISD with cGAS, the downstream pathway was triggered as STING disassociated from its location at the endoplasmic reticulum. Upon direct stimulation of pDCs by STING agonist 2'3' cGAMP or dsDNA, pDC-s produced type I, and type III IFN. Moreover, we documented that cGAS-STING-mediated IFN production is mediated by nuclear translocation of IRF3 whereas TLR9-mediated activation occurs through IRF7. Our data also indicate that pDC prestimulation of cGAS-STING dampened the TLR9-mediated IFN production. Furthermore, triggering of cGAS-STING induced expression of SOCS1 and SOCS3 in pDCs, indicating a possible autoinhibitory loop that impedes IFN production by pDCs. Thus, our study indicates that the cGAS-STING pathway exists in parallel to the TLR9-mediated DNA recognition in human pDCs with cross-talk between these two pathways.

Indexed as

Cyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDendritic CellsDNAEndoplasmic ReticulumHumansInterferon Regulatory Factor-3Interferon Regulatory Factor-7InterferonsMembrane ProteinsNucleotides, CyclicNucleotidyltransferasesPrimary Cell CultureSignal TransductionSTING ProteinSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteincGAS protein, humancyclic guanosine monophosphate-adenosine monophosphateCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNAInterferon Regulatory Factor-3Interferon Regulatory Factor-7InterferonsIRF3 protein, humanIRF7 protein, humanMembrane ProteinsNucleotides, CyclicNucleotidyltransferasesSOCS1 protein, humanSOCS3 protein, humanSTING1 protein, humanSTING ProteinSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteinTLR9 protein, humanToll-Like Receptor 9

Identifiers

PMID32471881
PMCPMC7460725
OpenAlexW3030603206

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.