Evidence map›Paper›PMID 27317904›Full record

ArticleThe American journal of pathology2016

CD4(+)CD25(hi)Foxp3(+) Cells Exacerbate Bleomycin-Induced Pulmonary Fibrosis.

Shirin Z Birjandi, Vyacheslav Palchevskiy, Ying Ying Xue, Stefanie Nunez, Rita Kern, S Sam Weigt, Joseph P Lynch, Talal A Chatila, John A Belperio

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
6.4field-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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. T Regulatory Mechanisms in Airway and Interstitial Lung Disease.Seminars in respiratory and critical care medicine · 2025
    Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Treg-tissue cell interactions in repair and regeneration.The Journal of experimental medicine · 2024
    Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Shirin Z BirjandiDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. Electronic address: shirin.birjandi@cshs.org.
Vyacheslav PalchevskiyDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
Ying Ying XueDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
Stefanie NunezDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
Rita KernDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
S Sam WeigtDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
Joseph P LynchDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
Talal A ChatilaDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts.
John A BelperioDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
University of California, Los Angeles · USHarvard University · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Molecular Basis of Hyper lgE ImmunodeficiencyR01AI065617 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Talal Amine Chatila · 2006 to 2026
$10.9M
Immune Mechanisms of AlloinjuryR01HL112990 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BELPERIO, JOHN A · 2012 to 2016
$2.2M
NCATS NIH HHS UL1 TR000124NHLBI NIH HHS R01 HL112990NIAID NIH HHS R01 AI065617
6 · The paper itself

Abstract

Idiopathic pulmonary fibrosis is a fatal lung disease with a median survival of 2 to 5 years. A decade of studies has downplayed inflammation contributing to its pathogenesis. However, these studies preceded the discovery of regulatory T cells (Tregs) and all of their functions. On the basis of human studies demonstrating Tregs can decrease graft-versus-host disease and vasculitides, there is consideration of their use to treat idiopathic pulmonary fibrosis. We hypothesized that Treg therapy would attenuate the fibroplasia involved in a preclinical murine model of pulmonary fibrosis. IL-2 complex was used in vivo to expand CD4(+)CD25(hi)Foxp3(+) cells in the lung during intratracheal bleomycin challenge; however, this unexpectedly led to an increase in lung fibrosis. More important, this increase in fibrosis was a lymphocyte-dependent process. We corroborated these results using a CD4(+)CD25(hi)Foxp3(+) cellular-based therapy. Mechanistically, we demonstrated that CD4(+)CD25(hi)Foxp3(+) cells undergo alterations during bleomycin challenge and the IL-2 complex had no effect on profibrotic (eg, transforming growth factor-β) or type 17 immune response cytokines; however, there was a marked down-regulation of the type 1 and augmentation of the type 2 immune response cytokines from the lungs. Collectively, our animal studies show that a specific lung injury can induce Treg alterations, which can augment pulmonary fibrosis.

Indexed as

Adoptive TransferAnimalsAntibiotics, AntineoplasticBleomycinDisease Models, AnimalFemaleFlow CytometryIdiopathic Pulmonary FibrosisMiceMice, Inbred C57BLMice, KnockoutReal-Time Polymerase Chain ReactionT-Lymphocytes, RegulatoryT-Lymphocyte SubsetsAntibiotics, AntineoplasticBleomycin

Identifiers

PMID27317904
PMCPMC4973661
OpenAlexW2441331071

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.