Kaiser Pete, Rothwell Lisa, Vasícek Dusan, Hala Karel
Institute for Animal Health, Compton, Berkshire, United Kingdom.
J Immunol. 2002 Apr 15;168(8):4216-20. doi: 10.4049/jimmunol.168.8.4216.
The obese strain (OS) of chickens, which suffers from spontaneous autoimmune thyroiditis, is an excellent animal model for Hashimoto's thyroiditis and provides a unique opportunity to investigate the mechanisms underlying and driving the onset of the disease. Following recent advances in cloning chicken cytokines, we can now begin to investigate the role of cytokines in driving the lymphoid infiltration of the thyroid seen in these birds from day 7 posthatch. Using real-time quantitative RT-PCR, we characterized the expression of IFN-gamma, IL-1beta, IL-2, IL-6, IL-8, IL-15, and IL-18 in thyroids from OS birds and control CB line birds, both in the embryo just before hatch (embryonic day 20) and at 3 and 5 days posthatch. All of these cytokines were up-regulated compared with levels in thyroids from CB birds, at least at some time points, with some evidence for coordination of regulation, e.g., for the proinflammatory cytokines IL-1beta and IL-8. Only IL-15 was up-regulated at all time points. IL-15 was also shown to be up-regulated in spleens of OS birds at embryonic day 20 and 5 days posthatch, suggesting that IL-15 is constitutively up-regulated in this line of birds. This could explain the general immune system hyperreactivity exhibited by OS chickens and may be a factor driving the lymphoid infiltration of the thyroid.
肥胖品系(OS)鸡患有自发性自身免疫性甲状腺炎,是桥本甲状腺炎的优良动物模型,为研究该疾病发病的潜在机制提供了独特机会。随着鸡细胞因子克隆技术的最新进展,我们现在可以开始研究细胞因子在驱动这些雏鸡自孵化后第7天出现的甲状腺淋巴细胞浸润中的作用。利用实时定量逆转录聚合酶链反应(RT-PCR),我们对OS品系鸡和对照CB品系鸡甲状腺中干扰素-γ(IFN-γ)、白细胞介素-1β(IL-1β)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-15(IL-15)和白细胞介素-18的表达进行了特征分析,这些样本分别来自孵化前(胚胎第20天)、孵化后3天和5天的雏鸡。与CB品系鸡甲状腺中的水平相比,所有这些细胞因子至少在某些时间点均上调,有证据表明存在调节协同作用,例如促炎细胞因子IL-1β和IL-8。只有IL-15在所有时间点均上调。IL-15在胚胎第20天和孵化后5天的OS品系鸡脾脏中也上调,表明IL-15在该品系鸡中持续上调。这可以解释OS鸡表现出的一般免疫系统高反应性,可能是驱动甲状腺淋巴细胞浸润的一个因素。