A critical role for lymphotoxin-beta receptor in the development of diabetes in nonobese diabetic mice.
A critical role for lymphotoxin-beta receptor in the development of diabetes in nonobese diabetic mice.
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DOI：
10.1084/jem.193.11.1333
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发表时间：
2001-06-04
影响因子：
15.3
通讯作者：
McDevitt, H O
中科院分区：
文献类型：
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作者：
Ettinger, R;Munson, S H;Chao, C C;Vadeboncoeur, M;Toma, J;McDevitt, H O
为探讨光氧素β受体（LTβR）在糖尿病发病机制中的作用，我们在非肥胖糖尿病（NOD）小鼠中表达了LTβR-Fc融合蛋白。该融合蛋白在胚胎中表达，在出生后的前2周达到高水平，然后随着年龄的增长而逐渐下降。高表达LTβR-Fc可阻断糖尿病的发生，但不能阻断胰岛炎的发生。在嵌合蛋白浓度下降后，小鼠变成糖尿病，动力学与对照相似。融合蛋白的早期表达导致脾脏结构破坏。然而，初级卵泡和滤泡树突状细胞，而不是边缘区，在老年小鼠的发展。因此，LTβR信号是糖尿病发展所必需的，并通过定性或定量不同的机制调节卵泡和边缘区结构。
To assess the role of lymphotoxin-β receptor (LTβR) in diabetes pathogenesis, we expressed an LTβR–Fc fusion protein in nonobese diabetic (NOD) mice. The fusion protein was expressed in the embryo, reached high levels for the first 2 wk after birth, and then declined progressively with age. High expression of LTβR–Fc blocked diabetes development but not insulitis. After the decline in chimeric protein concentration, mice became diabetic with kinetics similar to the controls. Early expression of fusion protein resulted in disrupted splenic architecture. However, primary follicles and follicular dendritic cells, but not marginal zones, developed in aged mice. Hence, LTβR signaling is required for diabetes development and regulates follicular and marginal zone structures via qualitatively or quantitatively distinct mechanisms.