Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease

EMBO Mol Med. 2014 Nov;6(11):1423-35. doi: 10.15252/emmm.201303376.

Abstract

The recent precipitous rise in autoimmune diseases is placing an increasing clinical and economic burden on health systems worldwide. Current therapies are only moderately efficacious, often coupled with adverse side effects. Here, we show that recombinant human insulin-like growth factor-1 (rhIGF-1) stimulates proliferation of both human and mouse regulatory T (Treg) cells in vitro and when delivered systemically via continuous minipump, it halts autoimmune disease progression in mouse models of type 1 diabetes (STZ and NOD) and multiple sclerosis (EAE) in vivo. rhIGF-1 administration increased Treg cells in affected tissues, maintaining their suppressive properties. Genetically, ablation of the IGF-1 receptor specifically on Treg cell populations abrogated the beneficial effects of rhIGF-1 administration on the progression of multiple sclerotic symptoms in the EAE model, establishing a direct effect of IGF-1 on Treg cell proliferation. These results establish systemically delivered rhIGF-1 as a specific, effective stimulator of Treg cell action, underscoring the clinical feasibility of manipulating natural tolerance mechanisms to suppress autoimmune disease.

Keywords: IGF‐1; T regulatory cells; autoimmunity; diabetes; multiple sclerosis.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Autoimmune Diseases / therapy*
  • Biological Therapy / methods
  • Cell Proliferation / drug effects*
  • Diabetes Mellitus, Experimental / therapy
  • Diabetes Mellitus, Type 1 / therapy
  • Disease Progression
  • Humans
  • Insulin-Like Growth Factor I / administration & dosage*
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Multiple Sclerosis / therapy
  • Recombinant Proteins / administration & dosage
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / physiology
  • Treatment Outcome

Substances

  • Recombinant Proteins
  • Insulin-Like Growth Factor I