Mehdi Najar1, Hussein Fayyad-Kazan2, Wissam H Faour3, Makram Merimi4,5, Etienne M Sokal6, Catherine A Lombard6, Hassan Fahmi1. 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. 2. Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences I, Lebanese University, Hadath, Lebanon. 3. Pharmacology, Gilbert and Rose-Mary Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon. wissam.faour@lau.edu.lb. 4. Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium. 5. Laboratory of Physiology, Ethnopharmacology and Genetics, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco. 6. Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale and Clinique (IREC), Université Catholique de Louvain, 1200, Brussels, Belgium.
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.
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.
Entities:
Keywords:
Co-culture; Cytokines; IL-23R; MSCs; ROR-γt; T cells; Th17
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