Evidence map›Paper›PMID 36031344›Full record

ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2022

IL-2 receptor engineering enhances regulatory T cell function suppressed by calcineurin inhibitor.

Toshihito Hirai, Po-Yu Lin, Teresa L Ramos, Federico Simonetta, Leon L Su, Lora K Picton, Jeanette Baker, Juliane K Lohmeyer, K Christopher Garcia, Robert S Negrin

Open access · bronzeAbstract read
In one paragraph

Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Review
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  4. Article
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  7. Review
  8. Regulatory T cells in dominant immunologic tolerance.The Journal of allergy and clinical immunology · 2024
    Review
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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

10 authors at 2 institutions in 2 countries.

Toshihito HiraiDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California, USA.ORCID 0000-0002-3343-6674
Po-Yu LinDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California, USA.
Teresa L RamosDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California, USA.ORCID 0000-0002-0696-7197
Federico SimonettaDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California, USA.
Leon L SuDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, California, USA.
Lora K PictonDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, California, USA.
Jeanette BakerDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California, USA.
Juliane K LohmeyerDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California, USA.
K Christopher GarciaDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, California, USA.
Robert S NegrinDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California, USA.
Stanford University · USTokyo Women's Medical University · JP

Funding

TLI/ATG CONDTIONING: KIDNEY/BLOOD STEM CELL TRANSPLANTSP01HL075462 · NHLBI · STANFORD UNIVERSITY · PI MEYER, EVERETT · 2004 to 2020
$27.9M
Structure-based engineering of immune cytokine signalingR01AI051321 · NIAID · STANFORD UNIVERSITY · PI Kenan Christopher GARCIA · 2002 to 2026
$5.6M
Structure, function and engineering of immune cytokine receptor signalingR37AI051321 · NIAID · STANFORD UNIVERSITY · PI GARCIA, KENAN CHRISTOPHER · 2013 to 2022
$4.2M
Designer Tregs for restoring tolerance in patients with type 1 diabetesUC4DK116264 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BLUESTONE, JEFFREY A, LIM, WENDELL A · 2017 to 2017
$3.4M
BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
Howard Hughes Medical InstituteNCRR NIH HHS S10 RR027431NHLBI NIH HHS P01 HL075462NIAID NIH HHS R01 AI051321NIAID NIH HHS R37 AI051321NIDDK NIH HHS UC4 DK116264NIH HHS P01 HL075462NIH HHS UC4DK116264
6 · The paper itself

Abstract

Clinical trials utilizing regulatory T cell (Treg) therapy in organ transplantation have shown promising results, however, the choice of a standard immunosuppressive regimen is still controversial. Calcineurin inhibitors (CNIs) are one of the most common immunosuppressants for organ transplantation, although they may negatively affect Tregs by inhibiting IL-2 production by conventional T cells. As a strategy to replace IL-2 signaling selectively in Tregs, we have introduced an engineered orthogonal IL-2 (ortho IL-2) cytokine/cytokine receptor (R) pair that specifically binds with each other but does not bind with their wild-type counterparts. Murine Tregs were isolated from recipients and retrovirally transduced with ortho IL-2Rβ during ex vivo expansion. Transduced Tregs (ortho Tregs) were transferred into recipient mice in a mixed hematopoietic chimerism model with tacrolimus administration. Ortho IL-2 treatment significantly increased the ortho IL-2Rβ(+) Treg population in the presence of tacrolimus without stimulating other T cell subsets. All the mice treated with tacrolimus plus ortho IL-2 achieved heart allograft tolerance, even after tacrolimus cessation, whereas those receiving tacrolimus treatment alone did not. These data demonstrate that Treg therapy can be adopted into a CNI-based regimen by utilizing cytokine receptor engineering.

Indexed as

Calcineurin InhibitorsTacrolimusAnimalsGraft SurvivalImmunosuppressive AgentsInterleukin-2MiceReceptors, Interleukin-2T-Lymphocytes, RegulatoryCalcineurin InhibitorsImmunosuppressive AgentsInterleukin-2Receptors, Interleukin-2Tacrolimusanimal models: murinebasic (laboratory) research/sciencebioengineeringcellular biologycytokines/cytokine receptorsimmunobiologyimmunosuppressant - calcineurin inhibitor (CNI)immunosuppression/immune modulationtolerance: chimerism

Identifiers

PMID36031344
PMCPMC10184573
OpenAlexW4293412929

What OpenQuestion holds

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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.