Evidence map›Paper›PMID 39302113›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2024

IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation.

Clancy W Mullan, Luanna Summer, Francesc Lopez-Giraldez, Zuzana Tobiasova, Thomas D Manes, Shruthi Yasothan, Guiyu Song, Daniel Jane-Wit, W Mark Saltzman, Jordan S Pober

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

10 authors.

Clancy W MullanDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.ORCID 0000-0002-2774-251X
Luanna SummerDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.ORCID 0009-0006-5188-9649
Francesc Lopez-GiraldezDepartment of Genetics, Yale School of Medicine, New Haven, CT.ORCID 0000-0001-7476-9822
Zuzana TobiasovaDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.
Thomas D ManesDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.
Shruthi YasothanDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.ORCID 0009-0001-0159-9006
Guiyu SongSection of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.ORCID 0000-0003-2617-9857
Daniel Jane-WitSection of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.ORCID 0000-0001-7115-0362
W Mark SaltzmanDepartment of Biomedical Engineering, Yale University, New Haven, CT.ORCID 0000-0002-2163-549X
Jordan S PoberDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.ORCID 0000-0001-5990-1071

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Ex Vivo Nanoparticle Drug Delivery Targeted to Human Allograft EndotheliumR01AI175206 · NIAID · YALE UNIVERSITY · PI JORDAN S POBER, W. Mark Saltzman · 2024 to 2026
$1.9M
Cancer Bioinformatics: Data analysis and method development for the Yale Cancer CenterR50CA265359 · NCI · YALE UNIVERSITY · PI Juan Francisco Lopez Giraldez · 2022 to 2026
$699k
Intracellular Membrane Attack Complexes and COVID-19 Immune HyperactivationR21AI178582 · NIAID · YALE UNIVERSITY · PI JANE-WIT, DANIEL · 2023 to 2024
$461k
Targeting complement-induced IL-15 trans-presentation by human endothelial cellsR21AI180187 · NIAID · YALE UNIVERSITY · PI POBER, JORDAN S · 2024 to 2025
$454k
Ex Vivo Nanoparticle Drug Delivery Targeted to Human Allograft EndotheliumR56AI175206 · NIAID · YALE UNIVERSITY · PI POBER, JORDAN S, SALTZMAN, W. MARK · 2023 to 2023
$418k
BLRD VA I01 BX005117HHS | NIH | National Cancer Institute (NCI) R50CA265359HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R21AI178582HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R21AI180187HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R56AI175206NCATS NIH HHS UL1 TR001863NCI NIH HHS R50 CA265359NIAID NIH HHS R01 AI175206NIAID NIH HHS R21 AI178582NIAID NIH HHS R21 AI180187NIAID NIH HHS R56 AI175206Thoracic Surgery Foundation (TSF) Resident Research FellowshipYale | YSM | Veterans Administration Medical Center, Yale School of Medicine (VAMC) I01BX005117
6 · The paper itself

Abstract

Expression of IL-15 on the surface of human graft endothelial cells (ECs) bound to the IL-15Rα subunit can increase the activation of CTLs, potentiating allograft rejection. Our previous work showed that surface expression of this protein complex could be induced by alloantibody-mediated complement activation through increased IL-1β synthesis, secretion, and autocrine/paracrine IL-1-mediated activation of NF-κB. In this article, we report that cultured human ECs express eight differently spliced IL-15 transcripts. Remarkably, IL-1β does not alter the expression level of any IL-15 transcript but induces surface expression independently of RNA polymerase II-mediated transcription while requiring new protein translation. Mechanistically, IL-1β causes an NF-κB-mediated reduction in the level of microRNA Let-7c-3p, thereby relieving a block of translation of IL-15 surface protein. Let7c-3p anti-miR can induce EC surface expression of IL-15/IL-15Rα in the absence of complement activation or of IL-1, enabling IL-15 transpresentation to boost CD8 T cell activation. Because of the complexity we have uncovered in IL-15 regulation, we recommend caution in interpreting increased total IL-15 mRNA or protein levels as a surrogate for transpresentation.

Indexed as

Endothelial CellsInterleukin-15Interleukin-1betaMicroRNAsProtein BiosynthesisCells, CulturedGene Expression RegulationGraft RejectionHumansInterleukin-15 Receptor alpha SubunitLymphocyte ActivationNF-kappa BTransplantationIL15 protein, humanInterleukin-15Interleukin-15 Receptor alpha SubunitInterleukin-1betaMicroRNAsmirnlet7 microRNA, humanNF-kappa B

Identifiers

PMID39302113
PMCPMC11493510

What OpenQuestion holds

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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.