Immunological modulation following bone marrow-derived mesenchymal stromal cells and Th17 lymphocyte co-cultures
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.
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.
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.
Our findings suggest that BM-MSCs significantly modulate the Th17 lymphocyte pathway in a complex manner.
KeywordsTh17 Cytokines ROR-γt MSCs T cells IL-23R Co-culture
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.
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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).
- 12.Najar M, Rouas R, Raicevic G, Boufker HI, Lewalle P, Meuleman N, et al. Mesenchymal stromal cells promote or suppress the proliferation of T lymphocytes from cord blood and peripheral blood: the importance of low cell ratio and role of interleukin-6. Cytotherapy. 2009;11:570–83.CrossRefGoogle Scholar
- 18.Tso GH, Law HK, Tu W, Chan GC, Lau YL. Phagocytosis of apoptotic cells modulates mesenchymal stem cells osteogenic differentiation to enhance IL-17 and RANKL expression on CD4+ T cells. Stem Cells. 2010;28:939–54.Google Scholar
- 30.Zheng Y, Sun L, Jiang T, Zhang D, He D, Nie H. TNFalpha promotes Th17 cell differentiation through IL-6 and IL-1beta produced by monocytes in rheumatoid arthritis. J Immunol Res 2014; 2014:385352.Google Scholar