Modulation of virus-induced innate immunity and type 1 diabetes by IL-1 blockade
Modulation of virus-induced innate immunity and type 1 diabetes by IL-1 blockade
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DOI：
10.1177/1753425913502242
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发表时间：
2014-08-01
期刊：
影响因子：
3.2
通讯作者：
Zipris, Danny
中科院分区：
文献类型：
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作者：
Hara, Naoko;Alkanani, Aimon K.;Zipris, Danny
我们使用Kilham大鼠病毒(KRV)诱导的1型糖尿病(T1D)的LEW1.WR1模型来验证在疾病进程早期阻断IL-1通路可以调节病毒诱导的先天免疫和防止疾病进展的假说。给予KRV加IL-1受体拮抗剂(阿纳金纳)治疗14d，可预防胰腺炎和T1D。Anakinra逆转了KRV诱导的全身炎症，感染后第5天，T细胞在脾和胰腺淋巴结内聚集。阻断IL-1可调节脾组织中IRF-7和IL-6基因的表达，以及血清中IL-12和IL-23的p40亚单位的表达。Anakinra不干扰LEW1.WR1大鼠从脾、胰腺淋巴结或血清中清除病毒的能力。与这些数据一致，在处理动物的脾和外周血中检测到正常水平的KRV特异性适应性免疫反应。最后，阻断IL-1通路逆转了KRV诱导的肠道细菌群落的调节。这些数据可能暗示IL-1途径与KRV感染导致胰岛破坏的早期机制直接相关，从而提出了在疾病进程早期阻断IL-1途径可能是预防疾病的有效治疗方法的假设。
We used the LEW1.WR1 model of Kilham rat virus (KRV)-induced type 1 diabetes (T1D) to test the hypothesis that blocking IL-1 pathways early in the course of the disease can modulate virus-induced innate immunity and prevent disease progression. Administering KRV plus IL-1 receptor antagonist (Anakinra) for 14d prevented insulitis and T1D. Anakinra reversed the KRV-induced systemic inflammation evidenced by the accumulation of T cells in the spleen and pancreatic lymph nodes on d 5 post-infection. Blocking IL-1 modulated the level of IRF-7 and IL-6 gene expression in the spleen and the p40 subunit of IL-12 and IL-23 in the serum. Anakinra did not interfere with the ability of LEW1.WR1 rats to clear the virus from the spleen, pancreatic lymph nodes or serum. Consistent with these data, normal levels of KRV-specific adaptive immune responses were detected in in the spleen and peripheral blood of the treated animals. Finally, blocking IL-1 pathways reversed the KRV-induced modulation of gut bacterial communities. The data may imply that IL-1 pathways are directly linked with early mechanisms whereby KRV infection leads to islet destruction, raising the hypothesis that blocking IL-1 pathways early in the course of the disease could be a useful therapeutic approach for disease prevention.