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PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction

The programmed cell death protein 1 (PD1) immune checkpoint prevents inflammatory tissue damage by inhibiting immune reactions. Understanding the relevance of cardiac PD1 signaling may provide new insights into the inflammatory events under baseline conditions and disease. Here, we demonstrate disti...

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Autores principales: Michel, Lars, Korste, Sebastian, Spomer, Armin, Hendgen-Cotta, Ulrike Barbara, Rassaf, Tienush, Totzeck, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321105/
https://www.ncbi.nlm.nih.gov/pubmed/35886878
http://dx.doi.org/10.3390/ijms23147533
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author Michel, Lars
Korste, Sebastian
Spomer, Armin
Hendgen-Cotta, Ulrike Barbara
Rassaf, Tienush
Totzeck, Matthias
author_facet Michel, Lars
Korste, Sebastian
Spomer, Armin
Hendgen-Cotta, Ulrike Barbara
Rassaf, Tienush
Totzeck, Matthias
author_sort Michel, Lars
collection PubMed
description The programmed cell death protein 1 (PD1) immune checkpoint prevents inflammatory tissue damage by inhibiting immune reactions. Understanding the relevance of cardiac PD1 signaling may provide new insights into the inflammatory events under baseline conditions and disease. Here, we demonstrate distinct immunological changes upon PD1 deficiency in healthy hearts and during reperfused acute myocardial infarction (repAMI). In PD1-deficient mice, upregulated inflammatory cytokines were identified under baseline conditions including cardiac interleukins and extracellular signal-related kinase 1/2 (ERK1/2). A murine in vivo repAMI model to determine inflammatory changes in the early phase showed downregulation of the ligand PDL1, paralleled by an endothelial injury, indicated by loss of the CD31 signal. Immunofluorescence imaging showed decreased PDL1 expression specifically in the infarct zone, highlighting an involvement in PDL1 in myocardial injury response. Pharmacological depletion of PD1 prior to repAMI did not alter the area of infarction but led to increased numbers of CD8(+) T cells in treated mice. We conclude that PD1/PDL1 signaling plays a significant role in healthy hearts and repAMI, emphasizing the relevance of adaptive immunity during myocardial injury. The findings highlight the risk for adverse outcomes from acute myocardial infarction in the growing group of patients receiving immune checkpoint inhibitor therapy.
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spelling pubmed-93211052022-07-27 PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction Michel, Lars Korste, Sebastian Spomer, Armin Hendgen-Cotta, Ulrike Barbara Rassaf, Tienush Totzeck, Matthias Int J Mol Sci Article The programmed cell death protein 1 (PD1) immune checkpoint prevents inflammatory tissue damage by inhibiting immune reactions. Understanding the relevance of cardiac PD1 signaling may provide new insights into the inflammatory events under baseline conditions and disease. Here, we demonstrate distinct immunological changes upon PD1 deficiency in healthy hearts and during reperfused acute myocardial infarction (repAMI). In PD1-deficient mice, upregulated inflammatory cytokines were identified under baseline conditions including cardiac interleukins and extracellular signal-related kinase 1/2 (ERK1/2). A murine in vivo repAMI model to determine inflammatory changes in the early phase showed downregulation of the ligand PDL1, paralleled by an endothelial injury, indicated by loss of the CD31 signal. Immunofluorescence imaging showed decreased PDL1 expression specifically in the infarct zone, highlighting an involvement in PDL1 in myocardial injury response. Pharmacological depletion of PD1 prior to repAMI did not alter the area of infarction but led to increased numbers of CD8(+) T cells in treated mice. We conclude that PD1/PDL1 signaling plays a significant role in healthy hearts and repAMI, emphasizing the relevance of adaptive immunity during myocardial injury. The findings highlight the risk for adverse outcomes from acute myocardial infarction in the growing group of patients receiving immune checkpoint inhibitor therapy. MDPI 2022-07-07 /pmc/articles/PMC9321105/ /pubmed/35886878 http://dx.doi.org/10.3390/ijms23147533 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Michel, Lars
Korste, Sebastian
Spomer, Armin
Hendgen-Cotta, Ulrike Barbara
Rassaf, Tienush
Totzeck, Matthias
PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction
title PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction
title_full PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction
title_fullStr PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction
title_full_unstemmed PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction
title_short PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction
title_sort pd1 deficiency modifies cardiac immunity during baseline conditions and in reperfused acute myocardial infarction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321105/
https://www.ncbi.nlm.nih.gov/pubmed/35886878
http://dx.doi.org/10.3390/ijms23147533
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