The Insulin Receptor Plays a Critical Role in T Cell Function and Adaptive Immunity

J Immunol. 2017 Mar 1;198(5):1910-1920. doi: 10.4049/jimmunol.1601011. Epub 2017 Jan 23.


T cell activation is an energy-demanding process fueled by increased glucose consumption and accompanied by upregulation of the insulin receptor (INSR). In this article, we report that silencing the INSR in inducible knockdown rats impairs selective T cell functions but not thymocyte development. Glucose transport and glycolysis in activated CD4+ T cells were compromised in the absence of the INSR, which was associated with alterations in intracellular signaling pathways. The observed metabolic defects coincided with reduced cytokine production, proliferation, and migration, as well as increased apoptosis of CD4+ T cells. The cytotoxicity of CD8+ T cells in response to alloantigens was also diminished under these conditions, whereas the frequency and suppressive capacity of regulatory T cells were unaffected. The observed impairments proved to be decisive in vivo because silencing of the INSR attenuated clinical symptoms in animal models of acute graft-versus-host disease and multiple sclerosis. Taken together, our results suggest that upregulation of the INSR on T cells following activation is required for efficient adaptive immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Apoptosis
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Differentiation
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • Glucose / metabolism
  • Glycolysis / immunology
  • Graft vs Host Disease / immunology
  • Lymphocyte Activation / immunology
  • Rats
  • Receptor, Insulin / deficiency*
  • Receptor, Insulin / genetics
  • Receptor, Insulin / physiology*
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Thymocytes / immunology
  • Thymocytes / physiology*


  • Cytokines
  • Receptor, Insulin
  • Glucose