Open AccessInsulin‐like growth factor‐1 stimulates regulatory T cells and suppresses autoimmune disease
Author(s) -
Bilbao Daniel,
Luciani Luisa,
Johannesson Bjarki,
Piszczek Agnieszka,
Rosenthal Nadia
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201303376
Subject(s) - nod , autoimmune disease , immunology , nod mice , growth factor , cancer research , autoimmunity , insulin like growth factor , multiple sclerosis , regulatory t cell , disease , medicine , receptor , immune tolerance , t cell , biology , immune system , diabetes mellitus , endocrinology , il 2 receptor , antibody
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 (rh IGF ‐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 . rh IGF ‐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 rh IGF ‐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 rh IGF ‐1 as a specific, effective stimulator of Treg cell action, underscoring the clinical feasibility of manipulating natural tolerance mechanisms to suppress autoimmune disease.