Recurrent Adrenergic Stress Provokes Persistent Myocarditis in PD-1–Deficient Mice

Hayashi, Tomohiro; Lim, Kenji Rowel Q.; Kovacs, Attila; Mann, Douglas L.

doi:10.1016/j.jacbts.2023.07.012

Cited by 3 publications

(6 citation statements)

References 39 publications

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“…178,[182][183][184] In addition, a recent preclinical study proposed adrenergic stress as a potential risk factor for ICI myocarditis, as PD-1 −/− mice developed autoimmune myocarditis with significant infiltration of CD8 + T cells following repeated in vivo administration of isoproterenol. 185 This needs further investigation, particularly in a clinical setting.…”

Section: Ici Myocarditismentioning

confidence: 99%

Autoimmune Myocarditis, Old Dogs and New Tricks

Won,

Song,

Kalinoski

et al. 2024

Circulation Research

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Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood. The emergence of myocarditis associated with immune checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity to understand autoimmune mechanisms in myocarditis, with autoreactive T cells specific for cardiac myosin playing a pivotal role. Despite their self-antigen recognition, cardiac myosin-specific T cells can be present in healthy individuals due to bypassing the thymic selection stage. In recent studies, novel modalities in suppressing the activity of pathogenic T cells including cardiac myosin-specific T cells have proven effective in treating autoimmune myocarditis. This review offers an overview of the current understanding of heart antigens, autoantibodies, and immune cells as the autoimmune mechanisms underlying various forms of myocarditis, along with the latest updates on clinical management and prospects for future research.

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Section: Ici Myocarditismentioning

confidence: 99%

Autoimmune Myocarditis, Old Dogs and New Tricks

Won,

Song,

Kalinoski

et al. 2024

Circulation Research

View full text Add to dashboard Cite

show abstract

“…Little is known about risk factors that may suddenly trigger myocarditis and subsequent cardiomyopathy, a rare disease in humans. In this issue of JACC: Basic to Translational Science , Hayashi et al 4 report that recurrent beta adrenergic stress by isoproterenol, a well characterized beta adrenergic receptor agonist, provoked a persistent myocarditis in PD-1–deficient mice. PD-1 deficiency in their mouse model mimicked ICI treatment in humans.…”

mentioning

confidence: 99%

“…In ICI blockade, anti–PD-1 antibody blocks the activity of PD-1, which is considered to be the brakes of the immune system, and which is turned off so that the tumor can be destroyed or controlled by a more robust immune response. Hayashi et al 4 provide an exciting and very thorough dissection of the cellular pathways by which PD-1 holds back the immune response against the heart in normal wild type (WT) mice while the deletion mutant PD-1–deficient strain, lacking functional PD-1, develops a CD8 + myocarditis, particularly in the female C57BL6 mouse model of the PD-1–deficient strain.…”

mentioning

confidence: 99%

“…The model from Hayashi et al 4 uses isoproterenol treatment in a regimen in which the model receives 3 priming low doses and then 1 final high-dose intraperitoneally 7 days of isoproterenol after the last priming dose. This neurohormonal stressor leads to myocarditis in only the PD-1–deficient strain of mice which is then characterized vs the WT which does not develop myocarditis.…”

mentioning

confidence: 99%

“…This would be risk from beta-receptor stimulation and activation of the beta receptors as was instituted in the mouse model in Hayashi et al. 4 The data suggest that there are other risk factors leading to inflammatory activation in the heart with cellular infiltration and cardiomyopathy in humans in addition to the strong risk factor PD-1 deficiency or ICI treatment. What would these risk factors look like?…”

mentioning

confidence: 99%

See 2 more Smart Citations

PD-1 Checkmate and the 2-Edged Sword of the Immune System

Cunningham,

Cooper

2023

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The Emerging Field of Cardioimmunology: Past, Present and Foreseeable Future

Mann

2024

Circulation Research

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Over the past 30 years, the field of cardioimmunology has moved from being dismissed as a field that was chasing an epiphenomenon of little biological consequence to a scientific discipline that is providing important new insights into the immunologic basis for hypertension, atherosclerosis, myocarditis, pericarditis, autoimmune heart disease, and heart failure. In this article, we will review the conceptual insights and technical breakthroughs that have allowed the field to move forward, as well as the clinical trials in the cardioimmunology space, to provide a historical context for the articles that will appear in the compendium that is focused on the interface between cardioimmunology, myocardial function, and disease.

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Recurrent Adrenergic Stress Provokes Persistent Myocarditis in PD-1–Deficient Mice

Cited by 3 publications

References 39 publications

Autoimmune Myocarditis, Old Dogs and New Tricks

Autoimmune Myocarditis, Old Dogs and New Tricks

PD-1 Checkmate and the 2-Edged Sword of the Immune System

The Emerging Field of Cardioimmunology: Past, Present and Foreseeable Future

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