Evidence map›Paper›PMID 19487420›Full record

ArticleThe Journal of experimental medicine2009

Cholera toxin inhibits IL-12 production and CD8alpha+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function.

Andrea la Sala, Jianping He, Leopoldo Laricchia-Robbio, Stefania Gorini, Akiko Iwasaki, Michael Braun, George S Yap, Alan Sher, Keiko Ozato, Brian Kelsall

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

26 citing papers in PubMed, 53 citations in OpenAlex.

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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

10 authors at 8 institutions in 3 countries.

Andrea la SalaLaboratory of Molecular and Cellular Immunology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, 00163 Rome, Italy.
Jianping He
Leopoldo Laricchia-Robbio
Stefania Gorini
Akiko Iwasaki
Michael Braun
George S Yap
Alan Sher
Keiko Ozato
Brian Kelsall
Laboratory of Molecular Genetics · PLNational Institutes of Health · USIstituti di Ricovero e Cura a Carattere Scientifico · ITIstituto di Ricovero e Cura a Carattere Scientifico San RaffaeleNational Institute of Allergy and Infectious Diseases · USThe University of Texas Health Science Center at Houston · USUniversity Hospital, Newark · USYale University · US

Funding

Immune Regulation In Toxoplasmosis And Other Opportunistic InfectionsZIAAI000579 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SHER, ALAN · 2009 to 2022
$7.8M
STUDIES ON IMMUNE REGULATION IN TOXOPLASMOSISZ01AI000579 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI SHER, ALAN · 1990 to 2008
$4.0M
REGULATION OF IL 12 PRODUCTION BY BETA 2 INTEGRINSZ01AI000809 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI KELSALL, BRIAN · 1997 to 2008
$902k
Intramural NIH HHS
6 · The paper itself

Abstract

Prior studies have demonstrated that cholera toxin (CT) and other cAMP-inducing factors inhibit interleukin (IL)-12 production from monocytes and dendritic cells (DCs). We show that CT inhibits Th1 responses in vivo in mice infected with Toxoplasma gondii. This correlated with low serum IL-12 levels and a selective reduction in the numbers of CD8alpha(+) conventional DCs (cDCs) in lymphoid organs. CT inhibited the function of interferon (IFN) regulatory factor (IRF) 8, a transcription factor known to positively regulate IL-12p35 and p40 gene expression, and the differentiation of CD8alpha(+) and plasmacytoid DCs (pDCs). Fluorescence recovery after photobleaching analysis showed that exposure to CT, forskolin, or dibutyryl (db) cAMP blocked LPS and IFN-gamma-induced IRF8 binding to chromatin. Moreover, CT and dbcAMP inhibited the binding of IRF8 to the IFN-stimulated response element (ISRE)-like element in the mouse IL-12p40 promoter, likely by blocking the formation of ISRE-binding IRF1-IRF8 heterocomplexes. Furthermore, CT inhibited the differentiation of pDCs from fms-like tyrosine kinase 3 ligand-treated bone marrow cells in vitro. Therefore, because IRF8 is essential for IL-12 production and the differentiation of CD8alpha(+) cDCs and pDCs, these data suggest that CT and other Gs-protein agonists can affect IL-12 production and DC differentiation via a common mechanism involving IRF8.

Indexed as

AnimalsCD8 AntigensCD8-Positive T-LymphocytesCell DifferentiationCells, CulturedCholera ToxinCyclic AMPDendritic CellsFemaleGTP-Binding Protein alpha Subunits, GsHumansInterferon-gammaInterferon Regulatory Factor-1Interferon Regulatory Factor-8Interferon Regulatory FactorsInterleukin-12CD8alpha antigenCD8 AntigensCholera ToxinCyclic AMPGTP-Binding Protein alpha Subunits, GsInterferon-gammaInterferon Regulatory Factor-1Interferon Regulatory Factor-8Interferon Regulatory FactorsInterleukin-12Interleukin-12 Subunit p40Irf1 protein, mouse

Identifiers

PMID19487420
PMCPMC2715075
OpenAlexW2125625534

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.