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

被引:99
作者
Bilbao, Daniel [1 ]
Luciani, Luisa [1 ]
Johannesson, Bjarki [1 ]
Piszczek, Agnieszka [1 ]
Rosenthal, Nadia [1 ,2 ,3 ]
机构
[1] European Mol Biol Lab EMBL, Mouse Biol Unit, Monterotondo, Italy
[2] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England
[3] Monash Univ, Australian Regenerat Med Inst, EMBL Australia, Clayton, Vic, Australia
关键词
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;
D O I
10.15252/emmm.201303376
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:1423 / 1435
页数:13
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