Evidence map›Paper›PMID 22988032›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2012

Kruppel-like factor 2 modulates CCR5 expression and susceptibility to HIV-1 infection.

Max W Richardson, Julie Jadlowsky, Chuka A Didigu, Robert W Doms, James L Riley

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 24% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 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 2 institutions in 1 country.

Max W RichardsonDepartment of Microbiology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Julie Jadlowsky
Chuka A Didigu
Robert W Doms
James L Riley
University of Pennsylvania · USCancer Research Institute · US

Funding

Targeting the PD-1 signaling pathway to rescue HIV T cell dysfunctionP01AI080192 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI · 2008 to 2012
$12.6M
TRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6M
Sequencing and Viral Evolution CoreU19AI082628 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI RILEY, JAMES L. · 2009 to 2013
$8.9M
Restoring HIV-1 Specific T cell ImmunityR01CA147795 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RILEY, JAMES L. · 2010 to 2014
$1.8M
NCI NIH HHS R01 CA147795NCI NIH HHS R01CA147795NIAID NIH HHS P01 AI080192NIAID NIH HHS T32 AI007632NIAID NIH HHS U19 AI082628NIAID NIH HHS U19AI082628
6 · The paper itself

Abstract

CCR5, a cell surface molecule critical for the transmission and spread of HIV-1, is dynamically regulated during T cell activation and differentiation. The molecular mechanism linking T cell activation to modulation of CCR5 expression remains undefined. Kruppel-like factor 2 (KLF2) is a transcription factor that promotes quiescence, survival, and in part by modulating chemokine receptor levels, induces homing to secondary lymphoid organs. Given the relationship between T cell activation and chemokine receptor expression, we tested whether the abundance of KLF2 after T cell activation regulates CCR5 expression and, thus, susceptibility of a T cell to CCR5-dependent HIV-1 strains (R5). We observed a strong correlation between T cell activation, expression of KLF2 and CCR5, and susceptibility to infection. To directly measure how KLF2 affects CCR5 regulation, we introduced small interfering RNA targeting KLF2 expression and demonstrated that reduced KLF2 expression also resulted in less CCR5. Chromatin immunoprecipitation assays identified KLF2 bound to the CCR5 promoter in resting but not CD3/28 activated T cells, suggesting that KLF2 directly regulates CCR5 expression. Introduction of KLF2 under control of a heterologous promoter could restore CCR5 expression and R5 susceptibility to CD3/28 costimulated T cells and some transformed cell lines. Thus, KLF2 is a host factor that modulates CCR5 expression in CD4 T cells and influences susceptibility to R5 infection.

Indexed as

Genetic Predisposition to DiseaseCCR5 Receptor AntagonistsCD4-Positive T-LymphocytesCell Line, TransformedDown-RegulationDrug Delivery SystemsHIV-1HIV InfectionsHumansKruppel-Like Transcription FactorsLymphocyte ActivationPrimary Cell CultureProtein BindingReceptors, CCR5Resting Phase, Cell CycleRNA, Small InterferingCCR5 Receptor AntagonistsKLF2 protein, humanKruppel-Like Transcription FactorsReceptors, CCR5RNA, Small Interfering

Identifiers

PMID22988032
PMCPMC3466370
OpenAlexW2110176379

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.