Severity of experimental autoimmune encephalomyelitis is unexpectedly reduced in mice born to vitamin D-deficient mothers
Severity of experimental autoimmune encephalomyelitis is unexpectedly reduced in mice born to vitamin D-deficient mothers
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DOI：
10.1016/j.jsbmb.2010.03.006
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发表时间：
2010-07-01
影响因子：
4.1
通讯作者：
Feron, Francois
中科院分区：
文献类型：
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作者：
de Abreu, Diana Andrea Fernandes;Ibrahim, El Cherif;Feron, Francois
越来越多的数据表明，维生素d是一种太阳诱导的激素，在多发性硬化症（MS）的病因中起着关键作用。值得注意的是，有研究表明，ms存在明显的出生季节效应。我们推测，妊娠期维生素D缺乏是ms的一个危险因素。为了验证这一假设，我们在C57BL/6雌性小鼠受孕前6周诱导维生素D缺乏，并持续到后代出生。与我们的预测相反，我们在这里表明，与对照后代相比，暴露于发展性维生素D缺乏症（DVD）的成年后代出现了显著的轻度和延迟的实验性自身免疫性脑脊髓炎（EAE）。利用反转录和实时荧光定量PCR技术，我们检测了22个候选转录物在免疫后第0天和第30天在脾脏、大脑和脊髓中的表达水平。我们在此报告，免疫后第（30）天，TNF、骨桥蛋白、H2-Eb在对照小鼠脊髓中过表达，IFN在DVD小鼠脊髓中未表达。神经系统和免疫系统之间的另一个差异是：IL4的表达仅在脾脏中失调。DVD小鼠症状严重程度的减轻可以部分解释为神经系统限制维生素D受体（VDR），两种热休克蛋白（HSP90, HSPa8）和FK506结合蛋白la （FKBP1a）在第0天的过度表达。我们的临床试验和分子研究结果一致表明，母体维生素D缺乏症会给胎儿留下印记，并改变后代对EAE的易感性。我们提出一个新的假设来解释我们意想不到的观察结果。(C) 2010 Elsevier Ltd.版权所有。
Accumulating data indicate that vitamin D. a sun-induced hormone, plays a key role in multiple sclerosis (MS) etiology. Notably, it has been shown that there is a remarkable season of birth effect in MS. We surmised that gestational vitamin D deficiency is a risk factor for MS. To test this hypothesis, a vitamin D deficiency was induced in C57BL/6 female mice 6 weeks prior to conception and prolonged until offspring birth. Contrary to our prediction, we show here that adult offspring exposed to developmental vitamin D deficiency (DVD) developed a striking milder and delayed experimental autoimmune encephalomyelitis (EAE), when compared to control offspring. Using reverse transcription and quantitative real-time PCR, we measured the expression level of 22 candidate transcripts in the spleen, the cerebrum and the spinal cord, at Day(0) and Day(30) post-immunization. We report here that, at Day(30) post-immunization, TNF,osteopontin, H2-Eb were over-expressed and IFN was under-expressed in the spinal cord of control mice and not in DVD mice. Another discrepancy between nervous and immune systems was observed: expression of IL4 was dysregulated exclusively in the spleen. Reduced symptom severity in DVD mice can partially be explained by a nervous system-restricted over-expression of vitamin D receptor (VDR), two heat shock proteins (HSP90, HSPa8) and FK506 binding protein la (FKBP1a), at Day(0). Our clinical test and molecular findings converge to indicate that maternal hypovitaminosis D imprints the foetus and alters the susceptibility of the offspring to EAE. We propose a new hypothesis to explain our unexpected observations. (C) 2010 Elsevier Ltd. All rights reserved.