Evidence map›Paper›PMID 39814100›Full record

ArticleThe American journal of pathology2025

Cytotoxic T-Lymphocyte-Associated Protein 4 Fused to a Modified Fragment of IgG1 Reduces Muscle Fiber Damage in a Model of Duchenne Muscular Dystrophy by Attenuating Proinflammatory Gene Expression in Myeloid Lineage Cells.

Michelle Wehling-Henricks, Su-Yin Kok, Haley Gamboa, Pranav Kannan, Connor Thomas, Ivan Flores, Steven S Welc, James G Tidball

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of pathology, 2025. 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

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

8 authors.

Michelle Wehling-HenricksDepartment of Integrative Biology and Physiology, University of California, Los Angeles, California.
Su-Yin KokDepartment of Integrative Biology and Physiology, University of California, Los Angeles, California.
Haley GamboaDepartment of Integrative Biology and Physiology, University of California, Los Angeles, California.
Pranav KannanDepartment of Integrative Biology and Physiology, University of California, Los Angeles, California; Molecular, Cellular and Integrative Physiology Program, University of California, Los Angeles, California.
Connor ThomasDepartment of Integrative Biology and Physiology, University of California, Los Angeles, California.
Ivan FloresMolecular, Cellular and Integrative Physiology Program, University of California, Los Angeles, California.
Steven S WelcDepartment of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana.
James G TidballDepartment of Integrative Biology and Physiology, University of California, Los Angeles, California; Molecular, Cellular and Integrative Physiology Program, University of California, Los Angeles, California; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California. Electronic address: jtidball@physci.ucla.edu.

Funding

Myeloid-cell mediated mechanisms driving muscle growth and regenerationR01AR066036 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIDBALL, JAMES G · 2014 to 2018
$1.8M
Developing co-stimulatory blockade as a therapeutic strategy for Duchenne muscular dystrophyR01NS109117 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIDBALL, JAMES G · 2019 to 2023
$1.7M
Novel mechanisms regulating muscle growth and regeneration: elucidating the Klotho/Jmjd3/Wnt axisR01AR075768 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIDBALL, JAMES G · 2020 to 2024
$1.7M
Targeting leukemia inhibitory factor to dystrophic muscle via a macrophage-specific transgeneF31AR071783 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FLORES, IVAN · 2017 to 2019
$114k
NIAMS NIH HHS F31 AR071783NIAMS NIH HHS R01 AR066036NIAMS NIH HHS R01 AR075768NINDS NIH HHS R01 NS109117
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) is a lethal, muscle-wasting, genetic disease that is greatly amplified by an immune response to the diseased muscles. The mdx mouse model of DMD was used to test whether the pathology can be reduced by treatment with a cytotoxic T-lymphocyte-associated protein 4 fused to a modified fragment of IgG1 (CTLA4-Ig) fusion protein that blocks costimulatory signals required for activation of T cells. CTLA4-Ig treatment reduced mdx sarcolemma lesions and reduced the numbers of activated T cells, macrophages, and antigen-presenting cells in mdx muscle and reduced macrophage invasion into muscle fibers. In vitro data showed that CTLA4-Ig acts directly on bone marrow cells and macrophages to modify their function and gene expression. CTLA4-Ig treatment of mdx bone marrow cells diminished their mobility and chemotactic response to chemokine ligand-2. Treating mdx macrophages with CTLA4-Ig reduced their cytolysis of muscle cells in vitro. RNA-sequencing analysis of mdx macrophages showed that CTLA4-Ig reduced expression of genes associated with leukocyte chemotaxis, migration, and extravasation; >90% of those affected genes were tumor necrosis factor-α target genes. Comparison of mdx and wild-type macrophages by RNA sequencing showed that 46% of the genes down-regulated by CTLA4-Ig were genes up-regulated in macrophages by the presence of muscular dystrophy in mice. These findings show that CTLA4-Ig is a promising immunotherapeutic for DMD, and many of its beneficial effects may result from direct actions on macrophages that modify their expression of proinflammatory genes.

Indexed as

AbataceptCTLA-4 AntigenImmunoglobulin GMuscle Fibers, SkeletalMuscular Dystrophy, DuchenneMyeloid CellsRecombinant Fusion ProteinsAnimalsDisease Models, AnimalGene Expression RegulationInflammationMacrophagesMaleMiceMice, Inbred C57BLMice, Inbred mdxAbataceptCTLA-4 AntigenImmunoglobulin GRecombinant Fusion Proteins

Identifiers

PMID39814100
PMCPMC11959425

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.