Suppression of Autoimmune Diabetes by Soluble Galectin-1
Suppression of Autoimmune Diabetes by Soluble Galectin-1
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DOI：
10.4049/jimmunol.0800839
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Morelli, Adrian E.
中科院分区：
文献类型：
--
作者：
Perone, Marcelo J.;Bertera, Suzanne;Morelli, Adrian E.
1型糖尿病（T1D）是一种以胰腺β细胞为靶点的T细胞介导的自身免疫性疾病。我们研究了可溶性半乳糖凝集素-1 （gal-1）的能力，这是一种促进T细胞凋亡的内源性凝集素，可以下调破坏胰腺β细胞的T细胞反应。我们证明，在非肥胖糖尿病（NOD）小鼠中，gal-1治疗显著减少Th1细胞的数量，增加分泌胰岛细胞Ag特异性IL-A或IL-10的T细胞的数量，并导致p细胞反应性T细胞的外周缺失。在NOD小鼠的早期和亚临床阶段，给药gal-1可防止高血糖的发生（1,2）。预防性gal-1治疗将胰岛素的成分转变为不侵犯胰岛的浸润物，其中含有显著减少的Th1细胞数量和更高百分比的CD4(+) T细胞，含有IL-4、IL-5或IL-10。在NOD小鼠中，gal-1的有益作用与凝集素触发引起β细胞损伤的T细胞亚群凋亡的能力相关，同时保留幼稚T细胞、Th2淋巴细胞和调节性T细胞。重要的是，在持续T1D的NOD小鼠中，gal-1逆转了p细胞自身免疫和高血糖。由于在NOD小鼠中，gal-1治疗不会引起主要的副作用或β细胞毒性，因此使用gal-1来控制β细胞自身免疫是治疗亚临床或正在进行的T1D的一种新的选择。免疫学杂志，2009,32(2):2641-2653。
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the beta-cells of the pancreas. We investigated the ability (if soluble galectin-1 (gal-1), an endogenous lectin that promotes T cell apoptosis, to down-regulate the T cell response that destroys the pancreatic beta-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-A or IL-10 specific for islet cell Ag, and causes peripheral deletion of P-cell-reactive T cells. Administration or gal-1 prevented the onset of hyperglycemia in NOD mice at early and subclinical stages or 1, 11). 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 beta-cell damage while sparing naive T cells, Th2 lymphocytes, and regulatory T cells in NOD mice. Importantly, gal-1 reversed P-cell autoimmunity and hyperglycemia in NOD mice with ongoing T1D. Because gal-1 therapy did not cause major side effects or beta-cell toxicity in NOD mice, the use of gal-1 to control beta-cell autoimmunity represents a novel alternative for treatment of subclinical or ongoing T1D. The Journal of Immunology, 2009, 182: 2641-2653.