Use of a Cocktail Regimen Consisting of Soluble Galectin-1, Rapamycin and Histone Deacetylase Inhibitor May Effectively Prevent Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disorder that results in destruction of insulin-releasing β-cells of the pancreas. During the pathogenesis of T1D, at least two phases of β-cell death occur: an initiation event wherein macrophage-derived inflammatory cytokines induce β-cell necrosis and release of β-cell-specific antigens, and a second, antigen-driven event in which T-cell-mediated immune response is directed against β-cells. In contrast to macrophages and autoreactive T cells, regulatory T cells play a key role in inducing and maintaining immunological tolerance to self antigens. Therefore, modulation of the immune system may prevent the development of T1D. Herein, we proposed a cocktail regimen consisting of soluble galectin-1, rapamycin and histone deacetylase inhibitor (HDACi) for the treatment of T1D because (a) HDACi has been reported to protect against IL-1β-mediated loss in β-cell viability, (b) HDACi and rapamycin have the ability to promote the generation and function of regulatory T cells and thus suppress the cytotoxic T-cell function, and (c) administration of soluble galectin-1 can trigger apoptosis of the β-cell-reactive T cells. This cocktail regimen may not only block T-cell- and cytokine-mediated autoimmunity but also restore self-tolerance to β-cell antigens, therefore representing a novel alternative for treatment of T1D.