Insulin-Like Growth Factors Are Key Regulators of T Helper 17 Regulatory T Cell Balance in Autoimmunity

Daniel DiToro, Stacey N. Harbour, Jennifer K. Bando, Gloria Benavides, Steven Witte, Vincent A. Laufer, Carson Moseley, Jeffery R. Singer, Blake Frey, Henrietta Turner, Jens Bruning, Victor Darley-Usmar, Min Gao, Cheryl Conover, Robin D. Hatton, Stuart Frank, Marco Colonna, Casey T. Weaver

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Appropriate balance of T helper 17 (Th17) and regulatory T (Treg) cells maintains immune tolerance and host defense. Disruption of Th17-Treg cell balance is implicated in a number of immune-mediated diseases, many of which display dysregulation of the insulin-like growth factor (IGF) system. Here, we show that, among effector T cell subsets, Th17 and Treg cells selectively expressed multiple components of the IGF system. Signaling through IGF receptor (IGF1R) activated the protein kinase B-mammalian target of rapamycin (AKT-mTOR) pathway, increased aerobic glycolysis, favored Th17 cell differentiation over that of Treg cells, and promoted a heightened pro-inflammatory gene expression signature. Group 3 innate lymphoid cells (ILC3s), but not ILC1s or ILC2s, were similarly responsive to IGF signaling. Mice with deficiency of IGF1R targeted to T cells failed to fully develop disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Thus, the IGF system represents a previously unappreciated pathway by which type 3 immunity is modulated and immune-mediated pathogenesis controlled.

Original languageEnglish (US)
Pages (from-to)650-667.e10
JournalImmunity
Volume52
Issue number4
DOIs
StatePublished - Apr 14 2020

Keywords

  • CD4 T cell
  • EAE
  • IGF1R
  • Th17
  • Treg
  • insulin-like growth factor
  • multiple sclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Insulin-Like Growth Factors Are Key Regulators of T Helper 17 Regulatory T Cell Balance in Autoimmunity'. Together they form a unique fingerprint.

  • Cite this

    DiToro, D., Harbour, S. N., Bando, J. K., Benavides, G., Witte, S., Laufer, V. A., Moseley, C., Singer, J. R., Frey, B., Turner, H., Bruning, J., Darley-Usmar, V., Gao, M., Conover, C., Hatton, R. D., Frank, S., Colonna, M., & Weaver, C. T. (2020). Insulin-Like Growth Factors Are Key Regulators of T Helper 17 Regulatory T Cell Balance in Autoimmunity. Immunity, 52(4), 650-667.e10. https://doi.org/10.1016/j.immuni.2020.03.013