mTOR Signaling and Metabolic Regulation of T Cells: New Potential Therapeutic Targets in Autoimmune Diseases

Marina      Pierdominici; Davide      Vacirca; Federica      Delunardo; Elena      Ortona

Abstract

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that forms a multisubunit complex with numerous protein partners and it regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. A central role for mTOR in regulating T cell homeostasis is emerging. In various autoimmune diseases abnormal functioning, differentiation and/or activation of T cells have been documented and recent studies have detailed anomalous activation of various signaling axes including the mTOR pathway in these cells. In this review we summarize recent studies on the involvement of mTOR in T cell differentiation and metabolism, supporting a key role for this molecule in providing a direct link between these two processes. We also describe how the mTOR pathway affects multiple molecular processes in autoimmune diseases and discuss the potential of targeting this pathway in these disorders.

Keywords: mTOR, T lymphocytes, metabolism, autophagy, autoimmune diseases, mTOR inhibitors, rapamycin, vitamin D, Systemic lupus erythematosus (SLE), cytokines