Adult T-cells impair neonatal cardiac regeneration
Dolejsi T, Delgobo M, Schuetz T, Tortola L, Heinze KG, Hofmann U, Frantz S, Bauer A, Ruschitzka F, Penninger JM, Ramos GC, Haubner BJ (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 43
Pages Range: 2698-2709
Journal Issue: 28
DOI: 10.1093/eurheartj/ehac153
Abstract
Aims: Newborn mice and humans display transient cardiac regenerative potential that rapidly declines postnatally. Patients who survive a myocardial infarction (MI) often develop chronic heart failure due to the heart's poor regeneration capacity. We hypothesized that the cardiac 'regenerative-to-scarring' transition might be driven by the perinatal shifts observed in the circulating T-cell compartment. Methods and results: Post-MI immune responses were characterized in 1- (P1) vs. 7-day-old (P7) mice subjected to left anterior descending artery ligation. Myocardial infarction induced robust early inflammatory responses (36h post-MI) in both age groups, but neonatal hearts exhibited rapid resolution of inflammation and full functional recovery. The perinatal loss of myocardial regenerative capacity was paralleled by a baseline increase in αβ-T cell (CD4+ and CD8+) numbers. Strikingly, P1-infarcted mice reconstituted with adult T-cells shifted to an adult-like healing phenotype, marked by irreversible cardiac functional impairment and increased fibrosis. Infarcted neonatal mice harbouring adult T-cells also had more monocyte-derived macrophage recruitment, as typically seen in adults. At the transcriptome level, infarcted P1 hearts that received isolated adult T-cells showed enriched gene sets linked to fibrosis, inflammation, and interferon-gamma (IFN-γ) signalling. In contrast, newborn mice that received isolated Ifng -/- adult T-cells prior to MI displayed a regenerative phenotype that resembled that of its age-matched untreated controls. Conclusion: Physiological T-cell development or adoptive transfer of adult IFN-γ-producing T-cells into neonates contributed to impaired cardiac regeneration and promoted irreversible structural and functional cardiac damage. These findings reveal a trade-off between myocardial regenerative potential and the development of T-cell competence.
Involved external institutions
Medizinische Universität Innsbruck
Austria (AT)
Universitätsklinikum Würzburg
Germany (DE)
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universitätsspital Zürich (USZ)
Switzerland (CH)
Österreichische Akademie der Wissenschaften
Austria (AT)
Austria (AT)
Universitätsklinikum Würzburg
Germany (DE)
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universitätsspital Zürich (USZ)
Switzerland (CH)
Österreichische Akademie der Wissenschaften
Austria (AT)
How to cite
APA:
Dolejsi, T., Delgobo, M., Schuetz, T., Tortola, L., Heinze, K.G., Hofmann, U.,... Haubner, B.J. (2022). Adult T-cells impair neonatal cardiac regeneration. European Heart Journal, 43(28), 2698-2709. https://doi.org/10.1093/eurheartj/ehac153
MLA:
Dolejsi, Theresa, et al. "Adult T-cells impair neonatal cardiac regeneration." European Heart Journal 43.28 (2022): 2698-2709.
BibTeX: Download