mTOR signaling in T cell immunity and autoimmunity

Int Rev Immunol. 2015 Jan;34(1):50-66. doi: 10.3109/08830185.2014.933957. Epub 2014 Jul 14.

Abstract

The mammalian target of rapamycin (mTOR), a phosphoinositide-3-kinase-related protein kinase, acts as a rheostat capable of integrating a variety of environmental cues in the form of nutrients, energy, and growth factors to modulate organismal processes and homeostasis. Recently, there is a growing appreciation of mTOR in adaptive immunity for its crucial roles in keeping a proper balance between T cell quiescence and activation. Under steady-state circumstances, mTOR is subtly inhibited by multiple mechanisms to maintain normal T cell homeostasis. Antigen recognition by naïve T cells leads to mTOR activation, which subsequently promotes the differentiation of these cells into distinct effector T cell subsets. This review focuses primarily on the recent literature with respect to the regulatory effects and mechanisms of mTOR signaling in dictating T cell fate, and discusses the therapeutic implications of mTOR modulation in T-cell-mediated autoimmunity.

Keywords: T cell immunity; autoimmunity; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity*
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / pathology
  • Autoimmunity*
  • Cell Differentiation
  • Cytokines / genetics
  • Cytokines / immunology
  • Energy Metabolism / immunology
  • Gene Expression Regulation
  • Homeostasis
  • Humans
  • Immunity, Innate
  • Immunologic Factors / therapeutic use
  • Lymphocyte Activation
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / immunology*

Substances

  • Cytokines
  • Immunologic Factors
  • MTOR protein, human
  • TOR Serine-Threonine Kinases