Evidence map›Paper›PMID 28254742›Full record

ArticleBlood2017

Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage infiltration and TGF-β production.

Jing Du, Katelyn Paz, Ryan Flynn, Ante Vulic, Tara M Robinson, Katie E Lineburg, Kylie A Alexander, Jingjing Meng, Sabita Roy, Angela Panoskaltsis-Mortari and 13 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
12.1field-weighted citation impact, top 1% 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

101 citing papers in PubMed, 151 citations in OpenAlex.

  1. Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023
    Trial
  2. Trial
  3. Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis. A Clinical Trial.American journal of respiratory and critical care medicine · 2021
    Trial
  4. Chronic graft-versus-host disease.Nature reviews. Disease primers · 2026
    Review
  5. Article
  6. Advances in treatment of chronic graft-versus-host disease.International journal of hematology · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

41 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 10 institutions in 2 countries.

Jing DuDivision of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN.
Katelyn PazDivision of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN.
Ryan FlynnDivision of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN.
Ante VulicDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, MD.
Tara M RobinsonDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, MD.
Katie E LineburgQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Kylie A AlexanderQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Jingjing MengDivision of Surgical Oncology, Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.
Sabita RoyDivision of Surgical Oncology, Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.
Angela Panoskaltsis-MortariDivision of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN.
Michael LoschiDivision of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN.
Geoffrey R HillQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Jonathan S SerodyLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
Ivan MaillardLife Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI.
David MiklosStanford Cancer Center, Stanford University School of Medicine, Stanford, CA.
John KorethDana-Farber Cancer Institute, Boston, MA; and.
Corey S CutlerDana-Farber Cancer Institute, Boston, MA; and.
Joseph H AntinDana-Farber Cancer Institute, Boston, MA; and.
Jerome RitzDana-Farber Cancer Institute, Boston, MA; and.
Kelli P MacDonaldQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Timothy W SchackerDepartment of Medicine, University of Minnesota, Minneapolis, MN.
Leo LuznikDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, MD.
Bruce R BlazarDivision of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN.
University of Minnesota Medical Center · USDana-Farber Cancer Institute · USQIMR Berghofer Medical Research Institute · AUJohns Hopkins University · USSylvester Comprehensive Cancer Center · USSidney Kimmel Comprehensive Cancer Center · USStanford University · USUniversity of Michigan–Ann Arbor · USUniversity of Minnesota · USUniversity of North Carolina at Chapel Hill · 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
THERAPEUTIC APPROACHES TO OVARIAN/BREAST CANCER--HIGH DOSE CHEMOTHERAPY AND ABMSP01CA047741 · NCI · DUKE UNIVERSITY · PI HASSELBLAD, VICTOR · 1990 to 2013
$19.5M
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
Notch Signaling in AlloimmunityR01AI091627 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI PEAR, WARREN S · 2011 to 2025
$6.0M
IMMUNOLOGY TRAINING PROGRAMT32AI007313 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Carla Rothlin · 1989 to 2026
$5.7M
Antifibrotic Therapy to Improve Immune reconstitution in HIVR01AI093319 · NIAID · UNIVERSITY OF MINNESOTA · PI SCHACKER, TIMOTHY W · 2011 to 2014
$2.8M
Augmenting Antitumor Immunity after AllograftingR01CA122779 · NCI · JOHNS HOPKINS UNIVERSITY · PI LUZNIK, LEO · 2008 to 2012
$1.5M
BAFF Pathology: Novel Therapeutic Targets in Chronic Graft versus Host DiseaseK08HL107756 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SARANTOPOULOS, STEFANIE · 2011 to 2014
$520k
Preclinical Drug Approaches to Chronic GVHD Prevention and TreatmentR01HL126530 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2015 to 2015
$210k
NCI NIH HHS P01 CA047741NCI NIH HHS P01 CA142106NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA122779NCI NIH HHS T32 CA009138NHLBI NIH HHS K08 HL107756NHLBI NIH HHS R01 HL126530NIAID NIH HHS P01 AI056299NIAID NIH HHS R01 AI091627NIAID NIH HHS R01 AI093319NIAID NIH HHS T32 AI007313
6 · The paper itself

Abstract

Allogeneic hematopoietic stem cell transplantation is hampered by chronic graft-versus-host disease (cGVHD), resulting in multiorgan fibrosis and diminished function. Fibrosis in lung and skin leads to progressive bronchiolitis obliterans (BO) and scleroderma, respectively, for which new treatments are needed. We evaluated pirfenidone, a Food and Drug Administration (FDA)-approved drug for idiopathic pulmonary fibrosis, for its therapeutic effect in cGVHD mouse models with distinct pathophysiology. In a full major histocompatibility complex (MHC)-mismatched, multiorgan system model with BO, donor T-cell responses that support pathogenic antibody production are required for cGVHD development. Pirfenidone treatment beginning one month post-transplant restored pulmonary function and reversed lung fibrosis, which was associated with reduced macrophage infiltration and transforming growth factor-β production. Pirfenidone dampened splenic germinal center B-cell and T-follicular helper cell frequencies that collaborate to produce antibody. In both a minor histocompatibility antigen-mismatched as well as a MHC-haploidentical model of sclerodermatous cGVHD, pirfenidone significantly reduced macrophages in the skin, although clinical improvement of scleroderma was only seen in one model. In vitro chemotaxis assays demonstrated that pirfenidone impaired macrophage migration to monocyte chemoattractant protein-1 (MCP-1) as well as IL-17A, which has been linked to cGVHD generation. Taken together, our data suggest that pirfenidone is a potential therapeutic agent to ameliorate fibrosis in cGVHD.

Indexed as

Hematopoietic Stem Cell TransplantationAllograftsAnimalsB-LymphocytesBronchiolitis ObliteransChemokine CCL2Disease Models, AnimalGraft vs Host DiseaseInterleukin-17MacrophagesMiceMice, Mutant StrainsPulmonary FibrosisPyridonesSkin DiseasesT-Lymphocytes, Helper-InducerCcl2 protein, mouseChemokine CCL2Il17a protein, mouseInterleukin-17pirfenidonePyridonesTransforming Growth Factor beta

Identifiers

PMID28254742
PMCPMC5418639
OpenAlexW2591918412

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.