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 beta-cells of the pancreas. During the pathogenesis of T1D, at least two phases of beta-cell death occur: an initiation event wherein macrophage-derived inflammatory cytokines induce beta-cell necrosis and release of beta-cell-specific antigens, and a second, antigen-driven event in which T-cell-mediated immune response is directed against beta-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-1beta-mediated loss in beta-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 beta-cell-reactive T cells. This cocktail regimen may not only block T-cell- and cytokine-mediated autoimmunity but also restore self-tolerance to beta-cell antigens, therefore representing a novel alternative for treatment of T1D.
Jiang
Gui-xing
GX
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Cui
Yun-fu
YF
Zhong
Xiang-yu
XY
Tai
Sheng
S
Liu
Wei
W
Wang
Zhi-dong
ZD
Shi
Yu-guang
YG
D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000517:prevention & control; D037483:Galectin 1 / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology; D020123:Sirolimus / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
D037483:Galectin 1; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus