Insulin-like growth factor 2 enhances regulatory T-cell functions and suppresses food allergy in an experimental model.

BACKGROUND: The functions of regulatory T (Treg) cells are important in immunity, and the regulatory mechanisms of Treg cell activities are not fully understood yet. OBJECTIVES: We sought to investigate the role of insulin-like growth factor (IGF) 2 in the upregulation of Treg cell function. METHODS: The expression of insulin-like growth factor 2 receptor (IGF2R) on T cells was assessed by using flow cytometry. Treg cell functions were evaluated by assessing the suppressor effect on proliferation of other effector T (Teff) cells. The effect of IGF2 on regulating Treg cell functions were evaluated with a cell-culture model and a food allergy mouse model. RESULTS: Expression of IGF2R was observed in more than 90% of murine and human Treg cells but in less than 10% of effector CD4(+) T cells. Activation of IGF2R and T-cell receptor induced marked Treg cell proliferation and release of TGF-ß from Treg cells, which enhanced Treg cell immune suppressor effects on other Teff cell activities and allergic inflammation in the intestine. CONCLUSIONS: Activation of IGF2R enhances Treg cell functions in suppressing other Teff cell activities and inhibiting allergic inflammation in the intestine.