Evidence mapPaperPMID 41770848Full record

ArticleBlood2026

BET inhibition blunts antibody production and macrophage-mediated fibrosis to restore lung function in murine cGVHD.

Rathan Kumar, Lotus Neidemire-Colley, Elizabeth A R Garfinkle, Camryn Steere, Simran Surana, Annie Murray, Giorgia Giordano, Olivia Martin, Emerson D Woodbury, Adithe Rivaldi and 15 more

Abstract read
In one paragraph

Article in Blood, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Rathan KumarDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.ORCID 0009-0007-4693-8319
Lotus Neidemire-ColleyDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Elizabeth A R GarfinkleSteve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH.ORCID 0000-0002-7292-4347
Camryn SteereDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Simran SuranaDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Annie MurrayDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Giorgia GiordanoDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Olivia MartinDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Emerson D WoodburyDivision of Cardiac Surgery, Department of Surgery, The Ohio State University, Columbus, OH.
Adithe RivaldiSteve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH.ORCID 0009-0008-3366-5670
Satishkumar SinghDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.ORCID 0000-0001-9957-9566
Kara CorpsDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH.
Katlyn LedererPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Malith KarunasiriDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Matthew W GorrDivision of Cardiac Surgery, Department of Surgery, The Ohio State University, Columbus, OH.ORCID 0000-0001-7561-6481
Loren E WoldDivision of Cardiac Surgery, Department of Surgery, The Ohio State University, Columbus, OH.ORCID 0000-0001-8155-0204
Lalit SehgalDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.ORCID 0000-0002-1151-5427
Kenneth J OestreichDepartment of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH.
Nicole R GrieselhuberDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Marcos J de LimaDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.ORCID 0000-0002-8568-4522
Bruce R BlazarDivision of Blood & Marrow Transplant & Cellular Therapy, University of Minnesota, Department of Pediatrics, Minneapolis, MN.ORCID 0000-0002-9608-9841
Ivan MaillardPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA.ORCID 0000-0003-1312-6748
Katherine E MillerSteve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH.
Hannah K ChoeDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Parvathi RanganathanDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.ORCID 0000-0003-4963-3629

Funding

The Patient-Reported Outcomes, Community-Engagement and Language (PRO-CEL) CoreP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · 1985 to 2025
$88.4M
Single Cell Analysis and ImmunogeneticsP01HL158505 · DANA-FARBER CANCER INST · 2025 to 2025
$2.6M
Developing novel therapies to improve blood stem cell transplantation outcomesR01HL163849 · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2025 to 2025
$630k
Targeting epigenetic regulation via Bromodomain and Extraterminal (BET) domain inhibition for treatment of GVHDR01CA252469 · OHIO STATE UNIVERSITY · 2025 to 2025
$415k
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA252469NHLBI NIH HHS P01 HL158505NHLBI NIH HHS R01 HL163849
6 · The paper itself

Abstract

abstractChronic graft-versus-host disease (cGVHD) significantly contributes to late mortality after allogeneic stem cell transplantation, with bronchiolitis obliterans syndrome (BOS) being a particularly lethal and treatment-resistant complication despite available therapies. Bromodomain and extraterminal (BET) proteins are epigenetic readers driving inflammatory transcriptional programs across multiple cell types. We hypothesized that BET inhibition would suppress inflammatory T and B cells and decrease macrophage polarization to a profibrotic phenotype, alleviating disease. In an established BOS cGVHD model, BET inhibition reduced germinal center (GC) formation and responses through a reduction of the CXCL13:CXCR5 axis and inflammatory T follicular helper/GC B cells in the spleen, along with a reduction in plasma cell infiltration within the lung. Mice with cGVHD had elevated pathogenic immunoglobulin G1 (IgG1) and IgM levels, both in circulation and deposited on lung tissue, which were attenuated under BET inhibition. Single-cell RNA-sequencing analysis revealed distinct cell states in the BOS lung vs control. In cGVHD mice, gene set enrichment analysis revealed the upregulation of profibrotic Arginase1 and Tgfb1 expression in alveolar macrophages (AM) and interstitial macrophages (IM), which was significantly reduced with BET inhibition. Furthermore, BET inhibition targeted lung-infiltrating M2 macrophages through the selective depletion of CD206+FcγR+ IM and AM, ultimately resulting in reduced collagen deposition and improved lung function. Our findings reveal a previously unrecognized mechanistic axis of BET regulation during cGVHD fibrosis and highlight BET inhibition as a promising therapeutic strategy.

Indexed as

Bronchiolitis Obliterans SyndromeGraft vs Host DiseaseLungMacrophagesMacrophages, AlveolarAnimalsArginaseChemokine CXCL13Disease Models, AnimalFibrosisGerminal CenterImmunoglobulin GImmunoglobulin MMiceMice, Inbred C57BLReceptors, CXCR5Arg1 protein, mouseArginaseChemokine CXCL13Cxcl13 protein, mouseCXCR5 protein, mouseImmunoglobulin GImmunoglobulin MReceptors, CXCR5Tgfb1 protein, mouseTransforming Growth Factor beta1

Identifiers

PMID41770848
PMCPMC13277660

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.