Heart encased in ice with glowing pathways.

Heart Health Hype: Does IL-23R Really Matter in Myocardial Infarction?

Jordan Keane in Health & Wellness December 2025 • 4 min read.

"New research dives deep into IL-23R signaling's role in heart attacks, challenging previous assumptions and offering clarity for future treatments."

Heart disease remains a leading cause of mortality worldwide, spurring continuous research into novel therapeutic targets. Among these, Interleukin (IL-)1 has shown promise. However, the roles of other inflammatory cytokines are less clear. One such cytokine, IL-23, has presented conflicting results in studies of cardiac ischemia, making its role uncertain.

IL-23 is a composite cytokine formed from p19 and p40 subunits, which bind to IL-23R and IL-12Rβ1 receptors. This binding initiates Jak/STAT, PI3K, and Ras/Raf/MAPK pathways, pivotal for immune responses. Prior studies have suggested both protective and detrimental effects of IL-23 in myocardial infarction, creating a therapeutic dilemma.

To resolve this ambiguity, researchers have developed mice deficient in IL-23R-Y416FAICD signaling. These mice were subjected to rigorous ischemia/reperfusion experiments to assess the impact of IL-23R signaling on heart function and recovery. This article breaks down the findings and explores the implications for future cardiac research and treatment strategies.

Unraveling the IL-23R Mystery: What Did the Study Really Find?

Heart encased in ice with glowing pathways.

The study employed comprehensive methods to evaluate the effects of IL-23R signaling deficiency. IL-23R-Y416FAICD mice underwent both closed- and open-chest ischemia/reperfusion experiments, mimicking clinical scenarios of heart attack and surgical interventions. Cardiac function was assessed through echocardiography, measuring key parameters such as ejection fraction, end-systolic volume, and end-diastolic volume. Additionally, the expression of α-smooth muscle actin (SMA) and hyaluronic acid (HA) were analyzed to gauge tissue remodeling and healing.

Gene regulation was also examined to identify changes in inflammatory and structural markers. The infarct size, a critical indicator of damage, was quantified using Gomori's trichrome staining. To further explore the therapeutic potential, wild-type mice were injected with IL-23 post-ischemia to observe any influence on the healing phase. The results consistently pointed to a lack of significant impact from IL-23R deficiency on myocardial ischemia/reperfusion injury.

Minimal Impact: Researchers found that IL-23R signaling deficiency did not substantially alter key parameters in mice experiencing ischemia.
Ejection Fraction: There were no major differences in ejection fraction, indicating that the heart's pumping efficiency remained largely unaffected.
Infarct Size: The size of the damaged heart tissue was similar in both IL-23R deficient and wild-type mice, suggesting IL-23R doesn't play a key role in tissue damage.
Gene Regulation: The expression of genes related to inflammation and tissue repair showed no significant changes, further reinforcing the lack of IL-23R influence.
SMA and HA Protein Expression: Critical markers for cardiac remodeling were not significantly altered, indicating that the healing process was similar in both groups.

These findings challenge previous studies that suggested a more prominent role for IL-23 in cardiac ischemia. The consistency of these results across various experimental conditions strengthens the conclusion that IL-23R signaling may not be a critical therapeutic target in myocardial infarction.

The Broader Implications: Where Does This Leave Cardiac Research?

While the study's findings may seem like a setback for IL-23R-targeted therapies, they provide valuable direction for future research. By demonstrating that IL-23R signaling is not a significant factor in myocardial ischemia/reperfusion injury, scientists can refocus their efforts on more promising pathways. This redirection is essential for developing effective treatments for heart disease. Future studies could explore alternative inflammatory targets or investigate the interplay between multiple cytokines in cardiac remodeling. Ultimately, a deeper understanding of these complex mechanisms will pave the way for more effective and targeted therapies.

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This article is based on research published under:

DOI-LINK: 10.1038/s41598-018-35188-8, Alternate LINK

Title: Il-23R Signaling Plays No Role In Myocardial Infarction

Subject: Multidisciplinary

Journal: Scientific Reports

Publisher: Springer Science and Business Media LLC

Authors: Erika Engelowski, Nastaran Fazel Modares, Simone Gorressen, Pascal Bouvain, Dominik Semmler, Christina Alter, Zhaoping Ding, Ulrich Flögel, Jürgen Schrader, Haifeng Xu, Philipp A. Lang, Jens Fischer, Doreen M. Floss, Jürgen Scheller

Published: 2018-11-20

Everything You Need To Know

What exactly is IL-23R and why has it been considered a potential therapeutic target for heart attacks (myocardial infarction)?

IL-23R, or Interleukin-23 Receptor, is a receptor that binds to the cytokine IL-23. This binding triggers signaling pathways like Jak/STAT, PI3K, and Ras/Raf/MAPK, which are crucial for immune responses. It was considered a potential therapeutic target because IL-23 has roles, both protective and detrimental, in myocardial infarction as suggested by earlier studies. Targeting IL-23R was thought to potentially modulate inflammation and improve outcomes after a heart attack. However, the precise role of IL-23R signaling in cardiac ischemia has been ambiguous, leading to conflicting results and prompting further investigation.

How did researchers investigate the role of IL-23R signaling in myocardial infarction within this recent study, and what were the key methods they used?

Researchers used mice deficient in IL-23R-Y416FAICD signaling to investigate the role of IL-23R in myocardial infarction. They subjected these mice to ischemia/reperfusion experiments that mimicked both heart attacks and surgical interventions. Cardiac function was assessed using echocardiography, measuring parameters like ejection fraction, end-systolic volume, and end-diastolic volume. They also analyzed the expression of α-smooth muscle actin (SMA) and hyaluronic acid (HA) to evaluate tissue remodeling, quantified infarct size using Gomori's trichrome staining, and examined gene regulation to identify changes in inflammatory and structural markers. Wild-type mice were also injected with IL-23 post-ischemia to observe its influence on the healing phase.

What were the main findings regarding the impact of IL-23R signaling deficiency on heart function and tissue damage after myocardial ischemia/reperfusion injury?

The study's main finding was that IL-23R signaling deficiency did not significantly impact heart function or tissue damage after myocardial ischemia/reperfusion injury. Specifically, researchers observed minimal changes in ejection fraction, indicating heart's pumping efficiency remained largely unaffected. The infarct size was similar in both IL-23R deficient and wild-type mice, suggesting that IL-23R doesn't play a significant role in tissue damage. Gene expression related to inflammation and tissue repair showed no substantial changes. Furthermore, the expression of α-smooth muscle actin (SMA) and hyaluronic acid (HA), critical markers for cardiac remodeling, was not significantly altered.

If IL-23R signaling isn't a critical therapeutic target in myocardial infarction, what are the implications for future cardiac research and the development of new treatments?

The finding that IL-23R signaling may not be a critical therapeutic target in myocardial infarction suggests that resources should be redirected to other more promising pathways. This encourages the exploration of alternative inflammatory targets or the investigation of the interplay between multiple cytokines in cardiac remodeling. By focusing on more impactful mechanisms, future research can pave the way for more effective and targeted therapies for heart disease. It is important to understand that while IL-23R may not be the primary driver of damage, other cytokines, such as Interleukin (IL-)1, may hold more promise.

Given that prior studies suggested both protective and detrimental effects of IL-23 in myocardial infarction, how do these new findings challenging the role of IL-23R signaling impact our understanding of inflammatory responses in heart disease?

These new findings challenge the notion that IL-23R signaling is a central player in the inflammatory responses following myocardial infarction. While previous studies proposed that IL-23 had conflicting roles, the current research indicates that its impact on cardiac ischemia/reperfusion injury may be minimal. This suggests the inflammatory cascade in heart disease is likely more complex, involving other cytokines and signaling pathways that may have a more dominant effect. This result doesn't completely negate the role of inflammation but calls for a more nuanced understanding of how different inflammatory mediators interact and contribute to cardiac remodeling and recovery.