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Immunological modulation following bone marrow-derived mesenchymal stromal cells and Th17 lymphocyte co-cultures

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Abstract

Objective and design

The objective of the study is to uncover the influence of human bone marrow-derived mesenchymal stem cells (BM-MSCs) on the generation of Th17 lymphocytes in co-cultures of both BM-MSCs and T cells.

Materials and methods

BM-MSCs, characterized according to the international society for cellular therapy (ISCT) criteria, were co-cultured with T cells isolated from peripheral blood. The expression levels of IL-17 receptor, RORγt and IL-23 receptor were evaluated using flow cytometry. The levels of cytokines involved in Th17 immunomodulation were measured using multiplex assay.

Treatment

Inflammatory primed and non-primed BM-MSCs were co-cultured with either activated or non-activated T cells either at (1/80) and (1/5) ratio respectively.

Results

MSC/T-cell ratio and inflammation significantly influenced the effect of BM-MSCs on the generation of Th17 lymphocytes. Cocultures of either primed or non-primed BM-MSCs with activated T cells significantly induced IL-17A-expressing lymphocytes. Interestingly, the expression of the transcription factor RORγt was significantly increased when compared to levels in activated T cells. Finally, both cell ratio and priming of BM-MSCs with cytokines substantially influenced the cytokine profile of BM-MSCs and T cells.

Conclusion

Our findings suggest that BM-MSCs significantly modulate the Th17 lymphocyte pathway in a complex manner.

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Acknowledgements

The authors thank Laurence Lagneaux for providing preparations of MSCs and Fatema Bouhtit for her technical assistance. The authors would like to also thank Noureddine Boukhatem for his helpful discussions. This project was supported by “Le Fonds National de la Recherche Scientifique, F.R.S.-FNRS”, the “Télévie” and the Canadian Institutes of Health Research (Grant MOP-130293). Furthermore, we would like to thank Bio-Rad Laboratories, Inc. for technical support during the study.

Author information

Author notes

  1. Mehdi Najar and Hussein Fayyad-Kazan contributed equally.

Authors and Affiliations

  1. Osteoarthritis Research Unit, Department of Medicine, University of Montreal Hospital Research Center (CRCHUM), 900 rue Saint-Denis, R11.424, Montreal, QC, H2X 0A9, Canada

    Mehdi Najar & Hassan Fahmi

  2. Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences I, Lebanese University, Hadath, Lebanon

    Hussein Fayyad-Kazan

  3. Pharmacology, Gilbert and Rose-Mary Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon

    Wissam H. Faour

  4. Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium

    Makram Merimi

  5. Laboratory of Physiology, Ethnopharmacology and Genetics, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco

    Makram Merimi

  6. Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale and Clinique (IREC), Université Catholique de Louvain, 1200, Brussels, Belgium

    Etienne M. Sokal & Catherine A. Lombard

Authors
  1. Mehdi Najar
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Contributions

All authors contributed to this work, all authors participated in the writing and drafting of the manuscript as well as critically reviewing it. WF, MN and HFK did the statistical analysis. WF, MN and HFK significantly contributed to the writing process. All authors read and agreed with the final format of the manuscript.

Corresponding author

Correspondence to Wissam H. Faour.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was conducted in accordance with the Declaration of Helsinki (1964) and the protocol and experiments were approved by the local ethics committee of the “Institut Jules Bordet” (Belgium).

Additional information

Responsible Editor: John Di Battista.

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Cite this article

Najar, M., Fayyad-Kazan, H., Faour, W.H. et al. Immunological modulation following bone marrow-derived mesenchymal stromal cells and Th17 lymphocyte co-cultures. Inflamm. Res. 68, 203–213 (2019). https://doi.org/10.1007/s00011-018-1205-0

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  • DOI: https://doi.org/10.1007/s00011-018-1205-0

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