Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection

Cell Metab. 2018 Dec 4;28(6):922-934.e4. doi: 10.1016/j.cmet.2018.08.003. Epub 2018 Aug 30.


T cells represent a critical effector of cell-mediated immunity. Activated T cells engage in metabolic reprogramming during effector differentiation to accommodate dynamic changes in energy demands. Here, we show that the hormone, insulin, and downstream signaling through its insulin receptor shape adaptive immune function through modulating T cell metabolism. T cells lacking insulin receptor expression (LckCre+ Insrfl/fl) show reduced antigen-specific proliferation and compromised production of pro-inflammatory cytokines. In vivo, T cell-specific insulin receptor deficiency reduces T cell-driven colonic inflammation. In a model of severe influenza infection with A/PR8 (H1N1), lack of insulin receptor on T cells curtails antigen-specific immunity to influenza viral antigens. Mechanistically, insulin receptor signaling reinforces a metabolic program that supports T cell nutrient uptake and associated glycolytic and respiratory capacities. These data highlight insulin receptor signaling as an important node integrating immunometabolic pathways to drive optimal T cell effector function in health and disease.

Keywords: T cell function; T cell metabolism; adaptive immunity; anti-viral immunity; insulin; insulin resistance; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Glycolysis / immunology
  • Humans
  • Immunity, Cellular / immunology*
  • Inflammation / immunology
  • Inflammation / virology
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza, Human / immunology*
  • Insulin / metabolism
  • Lymph Nodes
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections
  • Receptor, Insulin / genetics
  • Receptor, Insulin / immunology*
  • Signal Transduction
  • Spleen
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Antigens, CD
  • Cytokines
  • Insulin
  • INSR protein, human
  • Receptor, Insulin