摘要

OBJECTIVE:Many patients with long-standing type 1 diabetes have remaining functional β-cells. This study investigated immunological differences between patients with or without measurable remaining endogenous insulin production after ≥10 years duration of disease.
RESEARCH DESIGN AND METHODS:Patients (n = 113; ≥18 years of age) with type 1 diabetes and with disease duration of ≥10 years were recruited at Uppsala University Hospital. Residual β-cell function was determined with an ultrasensitive C-peptide ELISA. Circulating cytokines, including interleukin-35 (IL-35), were determined in plasma. Additional blood samples were collected from 14 of the identified C-peptide-positive patients and 12 of the C-peptide-negative patients, as well as from 15 healthy control subjects, and were used for immediate investigation of peripheral blood mononuclear cells.
RESULTS:The blood concentration of the cytokine IL-35 was markedly lower in C-peptide-negative patients, and this was associated with a simultaneous decrease in the proportion of IL-35+ regulatory T cells (Tregs), IL-35+ regulatory B cells, and IL-35-producing CD8+Foxp3+ cells. IL-35 has previously been shown to maintain the phenotype of Tregs, block the differentiation of T-helper 17 cells, and thereby dampen immune assaults to β-cells. We found that the proportions of IL-17a+ cells among the Tregs, CD4+ T cells, and CD8+ T cells were lower in the C-peptide-positive patients.
CONCLUSIONS:Patients with remaining endogenous β-cell function after >10 years duration of type 1 diabetes differ immunologically from other patients with long-standing type 1 diabetes. In particular, they have a much higher IL-35 production.

译文

目的: 许多长期患有 1 型糖尿病的患者都有剩余的功能性 β 细胞。本研究调查了疾病持续时间 ≥ 10 年后,有或没有可测量的剩余内源性胰岛素产生的患者之间的免疫学差异。
研究设计和方法: 在乌普萨拉大学医院招募了 1 型糖尿病和病程 ≥ 10 年的患者 (n = 113; ≥ 18 岁)。用超灵敏的 c肽 ELISA 测定残余 β 细胞功能。血浆中测定循环细胞因子,包括 interleukin-35 (IL-35)。额外的血样采集自 14 名已鉴定的 c肽阳性患者和 12 名 c肽阴性患者,以及 15 名健康对照受试者, 并用于外周血单个核细胞的即时调查。
结果: c肽阴性患者的细胞因子 IL-35 的血液浓度明显较低,这与 IL-35 调节性 T 细胞 (Tregs) 的比例同时下降有关, IL-35 调节性 b细胞,IL-35-producing CD8 Foxp3 细胞。IL-35 先前已被证明可以维持 Tregs 的表型,阻止辅助性 T 细胞 17 的分化,从而抑制对 β 细胞的免疫攻击。我们发现在 C-肽阳性患者中,Tregs 、 CD4 T 细胞和 CD8 T 细胞中 IL-17a 细胞的比例较低。
结论: 1 型糖尿病持续时间> 10 年后,内源性 β 细胞功能剩余的患者与其他长期 1 型糖尿病患者在免疫学上有所不同。特别是,他们对生产有更高 IL-35。

Interleukin 35

肿瘤 白细胞介素 临床研究术语
概述  :  

白细胞介素35(Interleukin 3,IL-35)是由调节性T细胞产生的细胞因子,是IL-12家族中的一员,2007年首次在EB病毒感染的B细胞中发现,在免疫抑制中起作用。它是一个由IL-12α链和IL-27β链组成的二聚体蛋白,分别由两个独立的基因IL-12A和EBI3编码。调节性T细胞分泌产生的IL-35抑制免疫细胞的炎症应答。IL-35不在组织中持续表达,但是在炎性刺激物激活后,编码IL-35的基因由血管内皮细胞、平滑肌细胞和单核细胞转录。   小鼠的研究

Interleukin   英 /ɪn'tə'lʊkɪn/   美 /ɪn'tə'lʊkɪn/

释    义   n. [生化] 白介素

例    句   To observe the effect of mizolastine on leukotriene B4(LTB4) and interleukin 5(IL 5) released by spleen lymphocytes of allergic mice challenged by ovalbumin(OVA). 观察咪唑斯汀对卵蛋白(OVA)致敏的小鼠脾淋巴细胞释放白三烯B4(LTB4)和白介素5(IL 5)的影响。

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