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Cited by 152Mesenchymal stem cell researchT-cell and B-cell ImmunologyMitochondrial Function and Pathology

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

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Luz-Crawford, Patricia, Hernandez, Javier, Djouad, Farida, Luque-Campos, Noymar, Caicedo, Andres, Carrère-Kremer, Séverine, Brondello, Jean-Marc, Vignais, Marie-Luce +2 more·2019·Stem Cell Research & Therapy
DOI 10.1186/s13287-019-1307-9PMC PMC6676586
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Abstract

BACKGROUND: 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. METHODS AND RESULTS: 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 MSCs (sMSCs) from patients with rheumatoid arthritis (RA) with Th17 cells, we found that compared with healthy BM-MSCs, mitochondrial transfer to Th17 cells was impaired in RA-sMSCs. Moreover, artificial mitochondrial transfer also significantly reduced IL-17 production by Th17 cells. CONCLUSIONS: The present study brings some insights into a novel mechanism of T cell function regulation through mitochondrial transfer from stromal stem cells. The reduced mitochondrial transfer by RA-sMSCs might contribute to the persistence of chronic inflammation in RA synovitis.

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  • Through IL-10, PD-1, and PGE2, mesenchymal stem cells prevent T cell development into T helper 1 and T helper 17 (pro-inflammatory) cells.

    “Through IL-10, PD-1, and PGE2, MSCs prevent T cell development into T helper (Th)1 and Th17 (pro-inflammatory) cells [85, 86].”

    From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [85]

    The Background (page unavailable) says MSCs prevent Th17 and Th1 differentiation in vitro and identifies PGE2 as one factor in that inhibitory effect. The References name a study of Th17 repression through the PD-1 pathway, but this paper does not establish IL-10 as a mechanism for preventing Th1 or Th17 differentiation. Its Discussion instead focuses on mitochondrial transfer. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Mitochondrial transfer from MSCs could promote the differentiation of CD4+ T cells into Tregs and suppress Th17 activity, contributing to immune suppression.

    “Furthermore, MT from MSCs could promote the differentiation of CD4 + T cells into Tregs and suppress Th17 activity, contributing to immune suppression [129, 130].”

    From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [130]

    The Results section reports that Th17 cells receiving MSC mitochondria showed more Treg markers, suggesting a regulatory phenotype, and that mitochondrial transfer reduced IL-17 production. The study examined a CD4+ Th17 subset, not CD4+ T cells generally, and the reported phenotype does not establish differentiation into Tregs. No page numbers are available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Luz-Crawford, P., Hernandez, J., Djouad, F., Luque-Campos, N., Caicedo, A., Carrère-Kremer, S., Brondello, J.-M., Vignais, M.-L., Pène, J., & Jorgensen, C.
Affiliations
Inserm (FR)
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2019-08-01
Volume
10
Issue
1
Pages
232-232
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/s13287-019-1307-9
PMC
PMC6676586
OpenAlex
W2964578086
Cited by
152
References
3
Citations by year
2026: 19 · 2025: 30 · 2024: 19 · 2023: 23 · 2022: 24 · 2021: 21 · 2020: 14 · 2019: 2
FWCI
8.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Agence Nationale pour la Recherche (ANR-14-CE12-0002, ANR-11-INSB-005)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
mesenchymal stem cells, Th17 cells, mitochondrial transfer, IL-17, immunosuppression, mitochondrial bioenergetics, oxygen consumption, regulatory T cells, rheumatoid arthritis, synovial stem cells, chronic inflammation, synovitis, bone marrow mesenchymal stem cells
MeSH terms
Arthritis, Rheumatoid, Bone Marrow Cells, Cells, Cultured, Humans, Mitochondria, Oxygen Consumption, Synovial Membrane, Tumor Necrosis Factor-alpha, Coculture Techniques, Interleukin-17, T-Lymphocytes, Regulatory, Th17 Cells, Mesenchymal Stem Cells

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