title: Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations.
abstract: Immunosuppressive drugs are widely used to treat undesirable immune reaction, however their clinical use is often limited by harmful side effects. The combined application of immunosuppressive agents with mesenchymal stem cells (MSCs) offers a promising alternative approach that enables the reduction of immunosuppressive agent doses and simultaneously maintains or improves the outcome of therapy. The present study aimed to determinate the effects of immunosuppressants on individual T cell subpopulations and to investigate the efficacy of MSC-based treatment combined with immunosuppressive drugs. We tested the effect of five widely used immunosuppressants with different action mechanisms: cyclosporine A, mycophenolate mofetil, rapamycin, and two glucocorticoids - prednisone and dexamethasone in combination with MSCs on mouse CD4+and CD8+lymphocyte viability and activation, Th17 (RORγt+), Th1 (T-bet+), Th2 (GATA-3+) and Treg (Foxp3+) cell proportion and on the production of corresponding key cytokines (IL-17, IFNγ, IL-4 and IL-10). We showed that MSCs modulate the actions of immunosuppressants and in combination with immunosuppressive drugs display distinct effect on cell activation and balance among different T lymphocytes subpopulations and exert a suppressive effect on proinflammatory T cell subsets while promoting the functions of anti-inflammatory Treg lymphocytes. The results indicated that MSC-based therapy could be a powerful strategy to attenuate the negative effects of immunosuppressive drugs on the immune system.
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 12843, Prague 2, Czech Republic.|Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Hajkova
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 12843, Prague 2, Czech Republic.|Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Hermankova
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 12843, Prague 2, Czech Republic.|Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic.
authors.forename: Eliska
authors.initials: E
authors.lastname: Javorkova
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 12843, Prague 2, Czech Republic.|Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Bohacova
authors.affiliation: Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Zajicova
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 12843, Prague 2, Czech Republic.|Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Holan
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 12843, Prague 2, Czech Republic. magdalena.krulova@natur.cuni.cz.|Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic. magdalena.krulova@natur.cuni.cz.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Krulova
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009173:Mycophenolic Acid / Q000494:pharmacology; D011241:Prednisone / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus
keywords: Immunomodulation; Immunosuppressive drugs; Mesenchymal stem cells; Stem cell therapy; T cells