Suppression of Autoimmune Diabetes by Soluble Galectin-1

Abstract

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the β-cells of the pancreas. We investigated the ability of soluble galectin-1 (gal-1), an endogenous lectin that promotes T cell apoptosis, to down-regulate the T cell response that destroys the pancreatic β-cells. We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount of Th1 cells, augments the number of T cells secreting IL-4 or IL-10 specific for islet cell Ag, and causes peripheral deletion of β-cell-reactive T cells. Administration of gal-1 prevented the onset of hyperglycemia in NOD mice at early and subclinical stages of T1D. Preventive gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets and that contained a significantly reduced number of Th1 cells and a higher percentage of CD4+ T cells with content of IL-4, IL-5, or IL-10. The beneficial effects of gal-1 correlated with the ability of the lectin to trigger apoptosis of the T cell subsets that cause β-cell damage while sparing naive T cells, Th2 lymphocytes, and regulatory T cells in NOD mice. Importantly, gal-1 reversed β-cell autoimmunity and hyperglycemia in NOD mice with ongoing T1D. Because gal-1 therapy did not cause major side effects or β-cell toxicity in NOD mice, the use of gal-1 to control β-cell autoimmunity represents a novel alternative for treatment of subclinical or ongoing T1D.

Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes

“…Blockade of IL-17 did not prevent autoimmune diabetes [44]. Moreover, we did not observe abundant IL-17-producing splenocytes in NOD mice [40].…”

Galectins: Key Players at the Frontiers of Innate and Adaptive Immunity

“…placenta, testis and tumors) and were further evidenced by the ability of this lectin to control pro-inflammatory cytokine synthesis, T-cell survival and immune cell activation (5,6). These observations were reinforced by numerous publications describing the ability of exogenous Gal1 to suppress T-cell-mediated autoimmune diseases and the key role of this lectin in tumor-cell evasion of immune responses (6)(7)(8)(9)(10)(11)(12)(13). Several studies have focused on the immunoregulatory effects of this endogenous lectin in a broad range of innate and adaptive immune functions (6).…”

Engineering galectin–glycan interactions for immunotherapy and immunomodulation

“…Toward this end, delivery of galectin-1 prevented the onset of hyperglycemia in non-obese diabetic (NOD) mice, a preclinical model for the T-cell-mediated autoimmune disease, Type 1 diabetes (T1D). 51 In particular, galectin-1 delivery reduced the number of Th1 cells, increased the number of T cells secreting anti-inflammatory cytokines (interleukin (IL)-4 and IL-10), and caused peripheral deletion of T cells reactive towards insulin-producing pancreatic b-cells. As a result, galectin-1 therapy prevented onset of hyperglycemia in NOD mice at early and subclinical stages of T1D, and also reversed b-cell autoimmunity and hyperglycemia in NOD mice with on-going T1D.…”