Mesenchymal stem cell repression of Th17 cells is triggered by mitochondrial transfer

Stem Cell Research & Therapy
Patricia Luz-CrawfordChristian Jorgensen

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells with broad immunosuppressive capacities. Recently, it has been reported that MSCs can transfer mitochondria to various cell types, including fibroblast, cancer, and endothelial cells. It has been suggested that mitochondrial transfer is associated with a physiological response to cues released by damaged cells to restore and regenerate damaged tissue. However, the role of mitochondrial transfer to immune competent cells has been poorly investigated. Here, we analyzed the capacity of MSCs from the bone marrow (BM) of healthy donors (BM-MSCs) to transfer mitochondria to primary CD4+CCR6+CD45RO+ T helper 17 (Th17) cells by confocal microscopy and fluorescent-activated cell sorting (FACS). We then evaluated the Th17 cell inflammatory phenotype and bioenergetics at 4 h and 24 h of co-culture with BM-MSCs. We found that Th17 cells can take up mitochondria from BM-MSCs already after 4 h of co-culture. Moreover, IL-17 production by Th17 cells co-cultured with BM-MSCs was significantly impaired in a contact-dependent manner. This inhibition was associated with oxygen consumption increase by Th17 cells and interconversion into T regulatory cells. Finally, by co-culturing human synovial ...Continue Reading

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Citations

Mar 27, 2020·Frontiers in Bioengineering and Biotechnology·Francesca VelardeAndrés Caicedo
Sep 10, 2020·Frontiers in Bioengineering and Biotechnology·Micaela BalcázarAndrés Caicedo
Jul 12, 2020·Scientific Reports·R A Contreras-LopezF Djouad
Jun 25, 2020·International Journal of Molecular Sciences·Jean NakhleMarie-Luce Vignais
Nov 13, 2020·The FEBS Journal·Camila Castillo FerrerGabriel Ichim
Feb 17, 2021·Signal Transduction and Targeted Therapy·Delin LiuJunjie Gao
Feb 27, 2021·Frontiers in Cell and Developmental Biology·Luise MüllerMarc Schmitz
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Marina O GomzikovaAlbert A Rizvanov
Sep 18, 2021·Transplant International : Official Journal of the European Society for Organ Transplantation·Mehdi Maanaoui, Julie Kerr-Conte

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Methods Mentioned

BETA
PCR
flow cytometry
biopsies
PMA
confocal microscopy

Software Mentioned

DIVA
Imaris Bitplane
MitoCeption
GraphPad Prism
GraphPad

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