Type I and II Interferon Receptors Differentially Regulate Type 1 Diabetes Susceptibility in Male Versus Female NOD Mice
Type I and II Interferon Receptors Differentially Regulate Type 1 Diabetes Susceptibility in Male Versus Female NOD Mice
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DOI：
10.2337/db18-0331
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发表时间：
2018-09-01
期刊：
影响因子：
7.7
通讯作者：
Unanue, Emil R.
中科院分区：
文献类型：
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作者：
Carrero, Javier A.;Benshoff, Nicholas D.;Unanue, Emil R.
干扰素在自身免疫性糖尿病中的作用，无论是致病性的还是保护性的，仍然存在争议。在此，我们研究了缺乏 I 型 (IFNAR) 或 II 型 (IFNGR) 干扰素受体的 NOD 小鼠的糖尿病进展情况，以及首次在缺乏这两种受体的小鼠（双敲除 [DKO]）中进行的研究。所有小鼠均在单一特定无病原体设施中饲养、饲养和监测，雌性糖尿病发病率高，雄性糖尿病发病率低。我们的期望是去除干扰素信号将减少自身免疫破坏。然而，对 IFNAR 和 IFNGR 缺陷型 NOD 小鼠的糖尿病发病率检查显示，雌性小鼠糖尿病发病率下降，而雄性小鼠糖尿病发病率上升。在 DKO 小鼠中，糖尿病仅发生在雌性小鼠中，且发病率降低且动力学延迟。这些结果表明，干扰素对依赖于性别的 1 型糖尿病风险具有积极和消极的调节作用。
The role of interferons, either pathogenic or protective, during autoimmune diabetes remains controversial. Herein, we examine the progression of diabetes in NOD mice lacking the type I (IFNAR) or type II (IFNGR) interferon receptor and, for the first time, in mice deficient in both receptors (double knockout [DKO]). All mice were bred, maintained, and monitored in a single specific pathogen-free facility with high female and low male diabetes incidence. Our expectation was that removal of interferon signaling would reduce autoimmune destruction. However, examination of diabetes incidence in the IFNAR- and IFNGR-deficient NOD mice showed a reduction in females and an increase in males. In DKO mice, diabetes occurred only in female mice, at decreased incidence and with delayed kinetics. These results show that interferons act as both positive and negative modulators of type 1 diabetes disease risk dependent on sex.