Cited by 272T-cell and B-cell ImmunologyMetabolism, Diabetes, and CancerImmune cells in cancer

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

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Tsai, Sue, Clemente-Casares, Xavier, Zhou, Angela C., Lei, Helena, Ahn, Jennifer J., Chan, Yi Tao, Choi, Okmi, Luck, Helen +6 more·2018·Cell Metabolism

Abstract

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+ Insr fl/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.

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Crossref · 10.1016/j.cmet.2018.08.003

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53 of 53 references verified0 citation errors · 0 not checkable

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  • Insulin is a critical mediator of adaptive immune effector function against respiratory infections.

    “Insulin is a critical mediator of adaptive immune effector function against respiratory infections172, and mTORC1 activation of S6 kinase blocks insulin signaling173,174.”

    From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [172]

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Authors
Tsai, S., Clemente-Casares, X., Zhou, A. C., Lei, H., Ahn, J. J., Chan, Y. T., Choi, O., Luck, H., Woo, M., Dunn, S. E., Engleman, E. G., Watts, T. H., Winer, S., & Winer, D. A.
Affiliations
  • University Health Network (CA)
  • University of Toronto (CA)
  • Stanford University (US)
  • St. Michael's Hospital (CA)
Corresponding author
  • Tsai, Sue
  • Winer, Daniel A.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2018-12
Volume
28
Issue
6
Pages
922-934.e4
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2888838300
Cited by
272
References
53
Citations by year
2026: 18 · 2025: 31 · 2024: 32 · 2023: 38 · 2022: 46 · 2021: 54 · 2020: 37 · 2019: 14 · 2018: 1
FWCI
11.86
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Canadian Institutes of Health Research (119414, 142708, 136884, 143250)
  • FDN (148385)
  • Canadian Diabetes Association (OG-3-15-5014, CS-5-12-3886)
  • Bickell Foundation
  • Banting and Best Diabetes Center Feasibility Operating
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
insulin receptor, T cell metabolism, immunometabolism, T cell immunity, colonic inflammation, influenza, glycolysis, mitochondrial respiration, nutrient uptake, inflammatory cytokines, T cell proliferation, insulin signaling
MeSH terms
Animals, Glycolysis, Humans, Immunity, Cellular, Inflammation, Influenza, Human, Insulin, Lymph Nodes, Lymphocyte Activation, Mice, Inbred C57BL, Orthomyxoviridae Infections, Receptor, Insulin, Spleen, T-Lymphocytes, Signal Transduction, Antigens, CD, T-Lymphocyte Subsets, Cytokines, Mice, Influenza A Virus, H1N1 Subtype

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