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

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. Synopsis: In this study, chronic recombinant human insulin-like growth factor-I (rhIGF-1) delivery is shown to mediate autoimmune suppression in three mouse models of autoimmune disease by stimulating Treg cells expansion, activation and migration into affected tissues. rhIGF-1 stimulates proliferation of both human and mouse Treg cells in vitro. rhIGF-1 administered systemically via continuous minipump delivery halts autoimmune disease progression in mouse models of Type 1 diabetes and multiple sclerosis. rhIGF-1 directly activates Treg cell proliferation by increasing Treg cell concentration in affected tissues as shown in a mouse model where the IGF-1 receptor was specifically ablated on Treg cells. In this study, chronic recombinant human insulin-like growth factor-I (rhIGF-1) delivery is shown to mediate autoimmune suppression in three mouse models of autoimmune disease by stimulating Treg cells expansion, activation and migration into affected tissues.