Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction

Serena Zacchigna (), Valentina Martinelli, Silvia Moimas, Andrea Colliva, Marco Anzini, Andrea Nordio, Alessia Costa, Michael Rehman, Simone Vodret, Cristina Pierro, Giulia Colussi, Lorena Zentilin, Maria Ines Gutierrez, Ellen Dirkx, Carlin Long, Gianfranco Sinagra, David Klatzmann and Mauro Giacca
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Serena Zacchigna: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Valentina Martinelli: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Silvia Moimas: Azienda Sanitaria Universitaria Integrata di Trieste
Andrea Colliva: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Marco Anzini: Azienda Sanitaria Universitaria Integrata di Trieste
Andrea Nordio: Azienda Sanitaria Universitaria Integrata di Trieste
Alessia Costa: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Michael Rehman: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Simone Vodret: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Cristina Pierro: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Giulia Colussi: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Lorena Zentilin: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Maria Ines Gutierrez: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Ellen Dirkx: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Carlin Long: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Gianfranco Sinagra: Azienda Sanitaria Universitaria Integrata di Trieste
David Klatzmann: Immunology-Immunopathology-Immunotherapy (i3)
Mauro Giacca: Azienda Sanitaria Universitaria Integrata di Trieste

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Cardiomyocyte proliferation stops at birth when the heart is no longer exposed to maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to promote maternal tolerance towards the fetus. Here, we report a role of Tregs in promoting cardiomyocyte proliferation. Treg-conditioned medium promotes cardiomyocyte proliferation, similar to the serum from pregnant animals. Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte proliferation. Treg depletion after myocardial infarction results in depressed cardiac function, massive inflammation, and scarce collagen deposition. In contrast, Treg injection reduces infarct size, preserves contractility, and increases the number of proliferating cardiomyocytes. The overexpression of six factors secreted by Tregs (Cst7, Tnfsf11, Il33, Fgl2, Matn2, and Igf2) reproduces the therapeutic effect. In conclusion, Tregs promote fetal and maternal cardiomyocyte proliferation in a paracrine manner and improve the outcome of myocardial infarction.

Date: 2018
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DOI: 10.1038/s41467-018-04908-z

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