mTORC2 in Thymic Epithelial Cells Controls Thymopoiesis and T Cell Development

J Immunol. 2016 Jul 1;197(1):141-50. doi: 10.4049/jimmunol.1502698. Epub 2016 May 27.

Abstract

Thymic epithelial cells (TECs) play important roles in T cell generation. Mechanisms that control TEC development and function are still not well defined. The mammalian or mechanistic target of rapamycin complex (mTORC)2 signals to regulate cell survival, nutrient uptake, and metabolism. We report in the present study that mice with TEC-specific ablation of Rictor, a critical and unique adaptor molecule in mTORC2, display thymic atrophy, which accompanies decreased TEC numbers in the medulla. Moreover, generation of multiple T cell lineages, including conventional TCRαβ T cells, regulatory T cells, invariant NKT cells, and TCRγδ T cells, was reduced in TEC-specific Rictor-deficient mice. Our data demonstrate that mTORC2 in TECs is important for normal thymopoiesis and efficient T cell generation.

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Epithelial Cells / physiology*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Subsets / immunology*
  • Lymphopoiesis*
  • Mechanistic Target of Rapamycin Complex 2
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocytes / immunology*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Thymus Gland / physiology*

Substances

  • Carrier Proteins
  • Multiprotein Complexes
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • rictor protein, mouse
  • Mechanistic Target of Rapamycin Complex 2
  • TOR Serine-Threonine Kinases