Aims

To assess the combination therapy of anti-CD20 mabs and adenovirus-mediated interleukin-10 (IL-10) gene delivery on the prevention of type 1 diabetes (T1D) in non-obese diabetes (NOD) mice.

Main methods

In present study, we simultaneously blocked the B cell interactions and recovered the Th cell subset proportion by using through anti-CD20 Mab and adenovirus-mediated gene delivery of IL-10, respectively. After 9 consecutive days of combination therapy, various measurements, including hematoxylin-eosin staining (HE), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay (TUNEL), immunohistochemistry, ELISA, PCR and western blot were applied to further assess the efficacy.

Key findings

The results suggested that the combination intervention reduced the T1D-associated morbidity of NOD mice, promote insulin secretion, control blood glucose and ease pancreatitis. Moreover, the combination therapy might play a protective role in pancreatic β cells by suppressing the expression of TNF-α and Fas, blocking the Caspase-8 and Caspase-3 apoptotic pathways and activating the Bcl-2 anti-apoptotic pathway. Finally, the combination intervention may up-regulate the gene expression of CK-19 and PDX-1 and further accelerate the differentiation and proliferation of pancreatic β cells.

Significance

Therefore, the combination intervention with anti-CD20 mabs and the IL-10 gene plays a role in the prevention of T1D to some extent in NOD mice.

中文翻译：

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抗CD20 mAb和IL-10基因的联合疗法可通过减轻胰腺炎和抑制NOD小鼠的凋亡来逆转1型糖尿病。

目的

评估抗CD20单抗和腺病毒介导的白介素10（IL-10）基因递送在非肥胖糖尿病（NOD）小鼠中预防1型糖尿病（T1D）的联合治疗。

主要方法

在本研究中，我们分别通过抗CD20单抗和腺病毒介导的IL-10基因传递来阻断B细胞相互作用并恢复Th细胞亚群的比例。联合治疗连续9天后，进行了各种测量，包括苏木精-伊红染色（HE），末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记测定（TUNEL），免疫组化，ELISA，PCR和Western blot来进一步评估功效。

主要发现

结果表明，联合干预可降低NOD小鼠的T1D相关发病率，促进胰岛素分泌，控制血糖并缓解胰腺炎。此外，联合治疗可能通过抑制TNF-α和Fas的表达，阻断Caspase-8和Caspase-3凋亡途径并激活Bcl-2抗凋亡途径而在胰腺β细胞中发挥保护作用。最后，联合干预可能上调CK-19和PDX-1的基因表达，并进一步促进胰腺β细胞的分化和增殖。

意义

因此，抗CD20单抗和IL-10基因的联合干预在一定程度上可预防NOD小鼠中的T1D。