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Journal of Translational Medicine

, 14:152

First Online: 31 May 2016Received: 15 February 2016Accepted: 18 May 2016DOI: 10.1186-s12967-016-0916-7

Cite this article as: Stallone, G., Infante, B., Di Lorenzo, A. et al. J Transl Med 2016 14: 152. doi:10.1186-s12967-016-0916-7


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.

KeywordsmTOR inhibitors Treg Dendritic cells Operational tolerance Transplantation Gianluigi Zaza and Giuseppe Grandaliano contributed equally to this work

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Author: Giovanni Stallone - Barbara Infante - Adelaide Di Lorenzo - Federica Rascio - Gianluigi Zaza - Giuseppe Grandaliano


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