mTORC1 signaling and IL-17 expression: Defining pathways and possible therapeutic targets

Eur J Immunol. 2016 Feb;46(2):291-9. doi: 10.1002/eji.201545886. Epub 2015 Dec 22.

Abstract

IL-17 mediates immune responses against extracellular pathogens, and it is associated with the development and pathogenesis of various autoimmune diseases. The expression of IL-17 is regulated by various intracellular signaling cascades. Recently, it has been shown that mechanistic target of rapamycin (mTOR) signaling, comprised mainly of mTORC1 signaling, plays a critical role in IL-17 expression. Here, we review the current knowledge regarding mechanisms by which mTORC1 regulates IL-17 expression. mTORC1 positively modulates IL-17 expression through several pathways, i.e. STAT3, -HIF-1α, -S6K1, and -S6K2. Amino acids (AAs) also regulate IL-17 expression by being the energy source for Th17 cells, and by activating mTORC1 signaling. Altogether, the AA-mTORC1-IL-17 axis has broad therapeutic implications for IL-17-associated diseases, such as EAE, allergies, and colitis.

Keywords: Amino acid ⋅ IL-17 ⋅ mTORC1 ⋅ STAT ⋅ HIF-1α.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy
  • Gene Expression Regulation
  • Humans
  • Hypersensitivity / immunology*
  • Hypersensitivity / therapy
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Mechanistic Target of Rapamycin Complex 1
  • Molecular Targeted Therapy
  • Multiprotein Complexes / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*
  • Th17 Cells / immunology*

Substances

  • Interleukin-17
  • Multiprotein Complexes
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases