Alleviating allergic airway diseases by means of short-term administration of IL-2 and dexamethasone

Abstract

IL-2 combined with dexamethasone can upregulate regulatory T (Treg) cells, but the mechanism is still under exploration. Although previous studies focused on upregulating Treg cells in normal mice, here we investigated whether the IL-2 and dexamethasone combination treatment can upregulate Treg cells in pathological conditions, specifically in alleviating allergic airway disease. We also examined the potential pathway involved in Treg cell upregulation by IL-2 and dexamethasone. We evaluated the dose of IL-2 and dexamethasone required to upregulate Treg cells in vivo and in vitro. We also tested IL-2 and dexamethasone in the intervention of allergic airway disease in a murine model. We found that administration of 400,000 IU of IL-2 and 0.1 mg of dexamethasone per mouse was effective in upregulating Treg cells, as well as in alleviating allergic airway disease in an established animal model, but this phenomenon disappeared after anti-CD25 antibody administration. We discovered that an in vitro low dose of IL-2 can protect Treg cells did not protect CD4(+)CD25(-) cells from dexamethasone-induced apoptosis by affecting forkhead box O3a phosphorylation through the Akt and serum and glucocorticoid-induced protein kinase pathways. IL-2/dexamethasone treatment can alleviate existing allergic airway diseases by upregulating Treg cells in vivo. Alow dose of IL-2 (10(-9) to 10(-11) mol/L) can protect Treg cells but not CD4(+)CD25(-) cells from dexamethasone-induced apoptosis in vitro, thereby explaining a possible mechanism of increased proportion of Treg cells.