Evidence map›Paper›PMID 28614794›Full record

ArticleJCI insight2017

An activated Th17-prone T cell subset involved in chronic graft-versus-host disease sensitive to pharmacological inhibition.

Edouard Forcade, Katelyn Paz, Ryan Flynn, Brad Griesenauer, Tohti Amet, Wei Li, Liangyi Liu, Giorgos Bakoyannis, Di Jiang, Hong Wei Chu and 17 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Pharmacodynamic Monitoring Predicts Outcomes of CCR5 Blockade as Graft-versus-Host Disease Prophylaxis.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2018
    Trial
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  20. Chronic GVHD: review advances in prevention, novel endpoints, and targeted strategies.Hematology. American Society of Hematology. Education Program · 2023
    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

27 authors at 10 institutions in 3 countries.

Edouard ForcadeDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Katelyn PazDivision of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Ryan FlynnDivision of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Brad GriesenauerDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Tohti AmetDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Wei LiDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Liangyi LiuDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Giorgos BakoyannisDepartment of Biostatistics, Indiana University Fairbanks School of Public Health and School of Medicine, Indiana, USA.
Di JiangNational Jewish Health, Denver, Colorado, USA.
Hong Wei ChuNational Jewish Health, Denver, Colorado, USA.
Mercedes LoberaGlaxoSmithKline, Cambridge, Massachusetts, USA.
Jianfei YangGlaxoSmithKline, Cambridge, Massachusetts, USA.
David S WilkesDean, University of Virginia, School of Medicine, Charlottesville, Virginia, USA.
Jing DuDivision of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Kate GartlanQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Geoffrey R HillQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Kelli Pa MacDonaldQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Eduardo L EspadaDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Patrick BlancoImmunoconcept, CNRS UMR 5164, Bordeaux University, Bordeaux, France.
Jonathan S SerodyLineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
John KorethDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Corey S CutlerDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Joseph H AntinDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Robert J SoifferDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Jerome RitzDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Sophie PaczesnyDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Bruce R BlazarDivision of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Harvard University · USIndiana University Health · USUniversity of Minnesota · USQIMR Berghofer Medical Research Institute · AUCentre National de la Recherche Scientifique · FRGlaxoSmithKline (United States) · USNational Jewish Health · USIndiana University – Purdue University Indianapolis · USUniversity of North Carolina at Chapel Hill · USUniversity of Virginia · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SHARPE, ARLENE H. · 2003 to 2023
$42.5M
Project 3: Humoral Targets and B Cell Biology in Chronic Graft-vs.-Host DiseaseP01CA142106 · NCI · DANA-FARBER CANCER INST · PI CUTLER, COREY S · 2009 to 2019
$17.5M
TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
IMMUNOLOGY TRAINING PROGRAMT32AI007313 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Carla Rothlin · 1989 to 2026
$5.7M
Manipulation of Immune Responsiveness after Hematopoietic Cell TransplantationR01CA183559 · NCI · DANA-FARBER CANCER INST · PI RITZ, JEROME, SOIFFER, ROBERT JON · 2013 to 2017
$3.7M
Translating Novel Drug-Targetable Biomarkers to Treat Graft versus Host DiseaseR01CA168814 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI PACZESNY, SOPHIE · 2013 to 2024
$3.0M
Reconstitution of Regulatory T Cells After Stem Cell TransplantationR01CA183560 · NCI · DANA-FARBER CANCER INST · PI RITZ, JEROME, SOIFFER, ROBERT JON · 2013 to 2017
$2.5M
Mechanistic Evaluations of ILC2 Cells for the Treatment/Prevention of GVHDR01HL139730 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SERODY, JONATHAN S. · 2017 to 2020
$2.2M
NCI NIH HHS P01 CA142106NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA168814NCI NIH HHS R01 CA183559NCI NIH HHS R01 CA183560NCI NIH HHS T32 CA009138NHLBI NIH HHS R01 HL139730NIAID NIH HHS P01 AI056299NIAID NIH HHS T32 AI007313
6 · The paper itself

Abstract

Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic stem cell transplantation requiring novel therapies. CD146 and CCR5 are expressed by activated T cells and associated with increased T cell migration capacity and Th17 polarization. We performed a multiparametric flow cytometry analysis in a cohort of 40 HSCT patients together with a cGvHD murine model to understand the role of CD146-expressing subsets. We observed an increased frequency of CD146+ CD4 T cells in the 20 patients with active cGvHD with enhanced RORγt expression. This Th17-prone subset was enriched for cells coexpressing CD146 and CCR5 that harbor mixed Th1/Th17 features and were more frequent in cGvHD patients. Utilizing a murine cGvHD model with bronchiolitis obliterans (BO), we observed that donor T cells from CD146-deficient mice versus those from WT mice caused significantly reduced pulmonary cGvHD. Reduced cGvHD was not the result of failed germinal center B cell or T follicular helper cell generation. Instead, CD146-deficient T cells had significantly lower pulmonary macrophage infiltration and T cell CCR5, IL-17, and IFN-γ coexpression, suggesting defective pulmonary end-organ effector mechanisms. We, thus, evaluated the effect of TMP778, a small-molecule RORγt activity inhibitor. TMP778 markedly alleviated cGvHD in murine models similarly to agents targeting the Th17 pathway, such as STAT3 inhibitor or IL-17-blocking antibody. Our data suggest CD146-expressing T cells as a cGvHD biomarker and suggest that targeting the Th17 pathway may represent a promising therapy for cGvHD.

Indexed as

ImmunologyTransplantation

Identifiers

PMID28614794
PMCPMC5470889
OpenAlexW2626820608

What OpenQuestion holds

Textmetadata
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.