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Diabetes：IL-2受体在1型糖尿病中发挥中枢性作用

2012-01-01 MedSci原创 MedSci原创

IL-2糖尿病
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近日，一项发表在Diabetes杂志上的一则研究"Central role for interleukin-2 in type 1 diabetes"证实IL-2在1型糖尿病中的关键性作用。 1型糖尿病临床表现为显著高血糖症，由进展性免疫介导的胰岛β细胞损伤及相关代谢功能障碍引起。如今遗传与免疫联合研究突出白细胞介素－2 (IL-2) 受体及其下游信号传导通路缺陷1型糖尿病发病机制中的中枢缺

近日，一项发表在Diabetes杂志上的一则研究"Central role for interleukin-2 in type 1 diabetes"证实IL-2在1型糖尿病中的关键性作用。

1型糖尿病临床表现为显著高血糖症，由进展性免疫介导的胰岛β细胞损伤及相关代谢功能障碍引起。如今遗传与免疫联合研究突出白细胞介素－2 (IL-2) 受体及其下游信号传导通路缺陷1型糖尿病发病机制中的中枢缺陷。

研究人员先前的动物模型干预研究提示：促进IL-2信号传导可预防及逆转疾病，主要由恢复调节性T细胞 (Treg) 的功能提供防护。在这项研究中，科学家着重于有IL-2信号传导缺陷的1型糖尿病的研究，并建立其促进该病的分子网络。该活动鉴定出一系列潜在新治疗靶标，这些新治疗靶标可通过促进IL-2通路而恢复1型糖尿病的适宜免疫调节。

 IL-2通过多种机制对免疫系统进行微调中具有独特作用，部分为通过其受体系统及下游信号传导通路的复杂调控而完成。发现疾病NOD小鼠模型及人中均存在 IL-2信号传导通路成分缺陷。虽然该通路中没有单独的遗传缺陷足以独立引起疾病，但该簇疾病相关性等位基因强烈提示：IL-2 通路作为整体在自身免疫性疾病的发生起作用。的确，直接促进该通路的治疗性干预有益于NOD小鼠的治疗，主要通过增强Treg的功能而发挥作用。

 IL-2 在人类治疗过程中强调合适剂量以避免系统性毒性并获预期转归很重要，在由T细胞介导的自身免疫性炎症中尤其重要。该细胞因子通过AICD激活的细胞收缩与Treg维护间达微妙平衡，这使其临床使用具有挑战性。IL-2过量会使平衡趋向于致病性自身反应性T细胞，允许其增殖超过Treg 的能力。Gc细胞因子家族冗余亦为IL-2 通路靶向的另一障碍。1型糖尿病中的成功通路靶向治疗可能必须涉及IL-2R 信号传导通路对多种免疫细胞作用的详尽了解，以指导通路特异性因子微调IL-2 反应——提供Treg支持，对激活的自体免疫性细胞予以缓冲。 （生物谷Bioon.com）

doi:10.2337/db11-1213
Central role for interleukin-2 in type 1 diabetes.

Hulme MA, Wasserfall CH, Atkinson MA, Brusko TM.

Type 1 diabetes presents clinically with overt hyperglycemia resulting from progressive immune-mediated destruction of pancreatic β-cells and associated metabolic dysfunction. Combined genetic and immunological studies now highlight deficiencies in both the interleukin-2 (IL-2) receptor and its downstream signaling pathway as a central defect in the pathogenesis of type 1 diabetes. Prior intervention studies in animal models indicate that augmenting IL-2 signaling can prevent and reverse disease, with protection conferred primarily by restoration of regulatory T-cell (Treg) function. In this article, we will focus on studies of type 1 diabetes noting deficient IL-2 signaling and build what we believe forms the molecular framework for their contribution to the disease. This activity results in the identification of a series of potentially novel therapeutic targets that could restore proper immune regulation in type 1 diabetes by augmenting the IL-2 pathway.

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    2012-03-30 ms9608593228839890

    #DIA#

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    2012-04-19 ms49895894946433513521

    #中枢性#

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    2012-04-22 木头人513

    #Diabetes#

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    2012-10-26 ms5439512287675881

    #BET#

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    2012-01-03 tomyang93

    #IL-2#

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