Injury polarized CD4
5 affiliations
- 1Aging+Cardiac Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA
- 2Lemole Center for Integrated Lymphatics and Vascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA
- 3Aging+Cardiac Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Department of Cellular and Molecular Medicine, Sarver Heart Center, University of Arizona, College of Medicine, Tucson, AZ, USA
- 4Center for Metabolic Disease Research and Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA
- 5Lemole Center for Integrated Lymphatics and Vascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Corresponding author. Temple University Lewis Katz School of Medicine 3500 N. Broad Street Medical Education Research Building, 10th Floor, Philadelphia, PA, 19140, USA.
Abstract
Myocardial infarction (MI) initiates a wound-healing response where immune cells shape inflammation, tissue repair, and long-term remodeling. Although CD4 + T cells are increasingly recognized as contributors to post-MI healing, the transcriptional reprogramming defining their early pro-reparative functions remains incompletely resolved. Here, RNA sequencing of cardiac CD4 + T cells isolated 1 week after MI found that a substantial post-MI transcriptional fraction lay outside canonical cytokine-induced T helper subset polarization, including type 1 T helper cell (Th1), Th2, Th17, nature-occurring CD4 + regulatory T cell (nTreg), and peripherally induced Treg (iTreg) reference transcriptomic programs. Instead, this response was organized into a distinct CD4 + Th tissue injury-polarized (CD4 +/TIP ) transcriptomic module enriched for extracellular matrix organization, adhesion, vascular, and developmental programs, with a coordinated downregulated arm involving RNA metabolism, chromatin regulation, and protein catabolic processes. Within the CD4 +/TIP population, MI induced and polarized at least 10 transcriptionally distinct CD4 + Th subsets at 1 week post-MI. Integration with curated transcription factors, epigenetic, reduction-oxidation (redox), and unfolded protein response (UPR) datasets identified a stress-adaptive architecture, in which regulatory subsets and the CD4 +/TIP population shared redox attenuation features, while the CD4 +/TIP state showed the strongest coupling to reparative tissue interaction programs, predominant Activating Transcription Factor 6 (ATF6)-aligned UPR structure, restrained proteostasis related outputs, and an innate-adjacent immune and secretome signature enriched for complement-associated, inflammatory recruitment, and extracellular communication genes. These findings identify a specific MI-associated CD4 + T-cell transcriptomic state during early MI inflammation and tissue repair. They establish a coordinated framework in which redox control, UPR, and tissue-injury-polarized CD4 + T-cell immune programs converge outside traditional Th and Treg lineages, offering new targets for CD4 + T-cell-mediated tissue repair after MI.
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BibTeX
@article{knight2026injury,
title = {{Injury polarized CD4}},
author = {Thomas WC. Knight and Fatma Saaoud and Ngefor Asangwe and Ying Shao and Iman Khan and Hajime Kubo and Mohsin Khan and Hong Wang and Raj Kishore and Xiaofeng Yang and Sadia Mohsin},
journal = {Redox Biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104383},
url = {https://doi.org/10.1016/j.redox.2026.104383},
note = {CC BY},
}
RIS
TY - JOUR
TI - Injury polarized CD4
AU - Thomas WC. Knight
AU - Fatma Saaoud
AU - Ngefor Asangwe
AU - Ying Shao
AU - Iman Khan
AU - Hajime Kubo
AU - Mohsin Khan
AU - Hong Wang
AU - Raj Kishore
AU - Xiaofeng Yang
AU - Sadia Mohsin
PY - 2026
DA - 2026/10/30
JO - Redox Biology
DO - 10.1016/j.redox.2026.104383
UR - https://doi.org/10.1016/j.redox.2026.104383
AB - Myocardial infarction (MI) initiates a wound-healing response where immune cells shape inflammation, tissue repair, and long-term remodeling. Although CD4 + T cells are increasingly recognized as contributors to post-MI healing, the transcriptional reprogramming defining their early pro-reparative functions remains incompletely resolved. Here, RNA sequencing of cardiac CD4 + T cells isolated 1 week after MI found that a substantial post-MI transcriptional fraction lay outside canonical cytokine-induced T helper subset polarization, including type 1 T helper cell (Th1), Th2, Th17, nature-occurring CD4 + regulatory T cell (nTreg), and peripherally induced Treg (iTreg) reference transcriptomic programs. Instead, this response was organized into a distinct CD4 + Th tissue injury-polarized (CD4 +/TIP ) transcriptomic module enriched for extracellular matrix organization, adhesion, vascular, and developmental programs, with a coordinated downregulated arm involving RNA metabolism, chromatin regulation, and protein catabolic processes. Within the CD4 +/TIP population, MI induced and polarized at least 10 transcriptionally distinct CD4 + Th subsets at 1 week post-MI. Integration with curated transcription factors, epigenetic, reduction-oxidation (redox), and unfolded protein response (UPR) datasets identified a stress-adaptive architecture, in which regulatory subsets and the CD4 +/TIP population shared redox attenuation features, while the CD4 +/TIP state showed the strongest coupling to reparative tissue interaction programs, predominant Activating Transcription Factor 6 (ATF6)-aligned UPR structure, restrained proteostasis related outputs, and an innate-adjacent immune and secretome signature enriched for complement-associated, inflammatory recruitment, and extracellular communication genes. These findings identify a specific MI-associated CD4 + T-cell transcriptomic state during early MI inflammation and tissue repair. They establish a coordinated framework in which redox control, UPR, and tissue-injury-polarized CD4 + T-cell immune programs converge outside traditional Th and Treg lineages, offering new targets for CD4 + T-cell-mediated tissue repair after MI.
SN - 2213-2317
ER -