Mesenchymal stem cells transfer mitochondria to allogeneic Tregs in an HLA-dependent manner improving their immunosuppressive activity

Karolina Piekarska, Zuzanna Urban-Wójciuk, Małgorzta Kurkowiak, Iwona Pelikant-Małecka, Adriana Schumacher, Justyna Sakowska, Jan Henryk Spodnik, Łukasz Arcimowicz, Hanna Zielińska, Bogusław Tymoniuk, Alicja Renkielska, Janusz Siebert, Ewa Słomińska, Piotr Trzonkowski, Ted Hupp and Natalia Maria Marek-Trzonkowska ()
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Karolina Piekarska: Medical University of Gdańsk
Zuzanna Urban-Wójciuk: International Centre for Cancer Vaccine Science, University of Gdańsk
Małgorzta Kurkowiak: International Centre for Cancer Vaccine Science, University of Gdańsk
Iwona Pelikant-Małecka: Medical University of Gdańsk
Adriana Schumacher: Medical University of Gdańsk
Justyna Sakowska: Medical University of Gdańsk
Jan Henryk Spodnik: Medical University of Gdańsk
Łukasz Arcimowicz: International Centre for Cancer Vaccine Science, University of Gdańsk
Hanna Zielińska: Medical University of Gdańsk
Bogusław Tymoniuk: Medical University of Łódź
Alicja Renkielska: Medical University of Gdańsk
Janusz Siebert: Medical University of Gdańsk
Ewa Słomińska: Medical University of Gdańsk
Piotr Trzonkowski: Medical University of Gdańsk
Ted Hupp: International Centre for Cancer Vaccine Science, University of Gdańsk
Natalia Maria Marek-Trzonkowska: Medical University of Gdańsk

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract Cell-based immunotherapies can provide safe and effective treatments for various disorders including autoimmunity, cancer, and excessive proinflammatory events in sepsis or viral infections. However, to achieve this goal there is a need for deeper understanding of mechanisms of the intercellular interactions. Regulatory T cells (Tregs) are a lymphocyte subset that maintain peripheral tolerance, whilst mesenchymal stem cells (MSCs) are multipotent nonhematopoietic progenitor cells. Despite coming from different origins, Tregs and MSCs share immunoregulatory properties that have been tested in clinical trials. Here we demonstrate how direct and indirect contact with allogenic MSCs improves Tregs’ potential for accumulation of immunosuppressive adenosine and suppression of conventional T cell proliferation, making them more potent therapeutic tools. Our results also demonstrate that direct communication between Tregs and MSCs is based on transfer of active mitochondria and fragments of plasma membrane from MSCs to Tregs, an event that is HLA-dependent and associates with HLA-C and HLA-DRB1 eplet mismatch load between Treg and MSC donors.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28338-0

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DOI: 10.1038/s41467-022-28338-0

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