Insulin‐like growth factor‐1 stimulates regulatory T cells and suppresses autoimmune disease
Author(s)
Bilbao, D
Luciani, L
Johannesson, B
Piszczek, A
Rosenthal, N
Type
Journal Article
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.
Date Issued
2014-10-22
Date Acceptance
2014-09-26
Citation
EMBO Molecular Medicine, 2014, 6 (11), pp.1423-1435
ISSN
1757-4676
Publisher
Wiley
Start Page
1423
End Page
1435
Journal / Book Title
EMBO Molecular Medicine
Volume
6
Issue
11
Copyright Statement
© 2014 The Authors. Published under the terms of the CC BY 4.0 license
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
autoimmunity
diabetes
IGF-1
multiple sclerosis
T regulatory cells
IGF-I
DIABETES-MELLITUS
PANCREATIC-ISLETS
PROTEIN-3 COMPLEX
GLYCEMIC CONTROL
GENE-EXPRESSION
IMMUNE-SYSTEM
NOD MOUSE
REG CELLS
MICE
IGF‐1
Administration, Intravenous
Animals
Autoimmune Diseases
Biological Therapy
Cell Proliferation
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 1
Disease Progression
Humans
Insulin-Like Growth Factor I
Mice, Inbred C57BL
Mice, Inbred NOD
Multiple Sclerosis
Recombinant Proteins
T-Lymphocytes, Regulatory
Treatment Outcome
06 Biological Sciences
11 Medical And Health Sciences
Publication Status
Published
Date Publish Online
2014-11-03