Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells
Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells
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DOI：
10.2337/diabetes.53.5.1303
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发表时间：
2004-05-01
期刊：
影响因子：
7.7
通讯作者：
Delovitch, TL
中科院分区：
文献类型：
--
作者：
Mi, QS;Ly, D;Delovitch, TL
在非肥胖型糖尿病（NOD）小鼠中，不变自然杀伤t细胞（iNKT细胞）数量和功能的缺乏与1型糖尿病的发病有关。α -半乳糖神经酰胺（α - galcer）激活cd1 -限制性iNKT细胞纠正了这些缺陷，并预防自发性和复发性1型糖尿病。尽管白细胞介素(IL)-4和IL-10与α - galcer诱导的1型糖尿病的保护有关，但这些细胞因子在iNKT细胞对1型糖尿病易感性的调节中的确切作用尚未确定。这里我们用NOD。IL-4（-/-）和NOD。IL-10（-/-）敲除小鼠进一步评估IL-4和IL-10在α - galcer诱导的1型糖尿病保护中的作用。我们发现IL-4而非IL-10表达介导对自发性1型糖尿病、复发性1型糖尿病和延长同基因胰岛移植功能的保护。胰腺淋巴结中转化生长因子- β基因表达的增加可能参与了α - galcer介导的NOD保护。IL-10（-/-）敲除小鼠。与维持iNKT细胞稳态所需的IL-7和IL-15不同，α - galcer诱导的iNKT细胞扩增和/或存活不需要IL-4和IL-10。我们的数据确定了IL-4在激活iNKT细胞抵抗1型糖尿病中的重要作用，这些发现对基于细胞因子的1型糖尿病治疗和胰岛移植具有重要意义。
In nonobese diabetic (NOD) mice, a deficiency in the number and function of invariant natural killer T-cells (iNKT cells) contributes to the onset of type 1 diabetes. The activation of CD1d-restricted iNKT cells by alpha-galactosylceramide (alpha-GalCer) corrects these deficiencies and protects against spontaneous and recurrent type 1 diabetes. Although interleukin (IL)-4 and IL-10 have been implicated in alpha-GalCer-induced protection from type 1 diabetes, a precise role for these cytokines in iNKT cell regulation of susceptibility to type I diabetes has not been identified. Here we use NOD.IL-4(-/-) and NOD.IL-10(-/-) knockout mice to further evaluate the roles of IL-4 and IL-10 in (alpha-GalCer-induced protection from type 1 diabetes. We found that IL-4 but not IL-10 expression mediates protection against spontaneous type 1 diabetes, recurrent type 1 diabetes, and prolonged syngeneic islet graft function. Increased transforming growth factor-beta gene expression in pancreatic lymph nodes may be involved in alpha-GalCer-mediated protection in NOD.IL-10(-/-) knockout mice. Unlike the requirement of IL-7 and IL-15 to maintain iNKT cell homeostasis, IL-4 and IL-10 are not required for alpha-GalCer-induced iNKT cell expansion and/or survival. Our data identify an important role for IL-4 in the protection against type 1 diabetes by activated iNKT cells, and these findings have important implications for cytokine-based therapy of type 1 diabetes and islet transplantation.