MTOR inhibitors effects on regulatory T cells and on dendritic cells. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Stallone, Giovanni; Infante, Barbara; Lorenzo, Adelaide; Rascio, Federica; Zaza, Gianluigi; Grandaliano, Giuseppe
• Is Part Of: Journal of translational medicine. Volume 14:Issue 1(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-12
• Subjects: mTOR inhibitors -- Treg -- Dendritic cells -- Operational tolerance -- Transplantation; Medicine, Experimental -- Periodicals; Human experimentation in medicine -- Periodicals; Therapeutics -- Periodicals; 615.50724
• DOI: 10.1186/s12967-016-0916-7
• Languages: English
• ISSNs: 1479-5876

Abstract

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 onTreg and DCs differentiation, activation, and function in the transplantation setting.