title: mTOR inhibitors effects on regulatory T cells and on dendritic cells.
abstract: The mammalian target of rapamycin (mTOR), a cytoplasmic serine/threonine kinase, represents a key biologic "switch" modulating cell metabolisms in response to environmental signals and is now recognized as a central regulator of the immune system. There is an increasing body of evidence supporting the hypothesis that mTOR inhibitors exhibit several biological properties in addition to immunosuppression, including anti-neoplastic effects, cardio-protective activities, and an array of immunomodulatory actions facilitating the development of an operational graft tolerance. The biological mechanisms explaining how mTOR inhibition can enable a tolerogenic state are still largely unclear. The induction of transplant tolerance might at the same time decrease rejection rate and minimize immunosuppression-related side effects, leading to an improvement in long-term graft outcome. In this scenario, T cell immunoregulation has been defined as the hallmark of peripheral tolerance. Two main immunologic cell populations have been reported to play a central role in this setting: regulatory T cells (Tregs) and dendritic cells (DCs). In this review we focus on mTOR inhibitors effects on Treg and DCs differentiation, activation, and function in the transplantation setting.
authors.affiliation: Nephrology, Dialysis and Tranplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 1, 71100, Foggia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stallone
authors.affiliation: Nephrology, Dialysis and Tranplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 1, 71100, Foggia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Infante
authors.affiliation: Nephrology, Dialysis and Tranplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 1, 71100, Foggia, Italy.
authors.forename: Adelaide
authors.initials: A
authors.lastname: Di Lorenzo
authors.affiliation: Nephrology, Dialysis and Tranplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 1, 71100, Foggia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Rascio
authors.affiliation: Renal Unit, Department of Medicine, University-Hospital of Verona, University of Verona, Piazzale A. Stefani 1, 37126, Verona, VR, Italy. gianluigi.zaza@univr.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zaza
authors.affiliation: Nephrology, Dialysis and Tranplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 1, 71100, Foggia, Italy. giuseppe.grandaliano@unifg.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008954:Models, Biological; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases
keywords: Dendritic cells; Operational tolerance; Transplantation; Treg; mTOR inhibitors