Sci Transl Med：MECP2复制影响免疫系统以及大脑发育

1999年，Huda Zoghbi博士和他的同事在贝勒医学院确定了Rett综合征（一种在出生后开始的神经系统疾病，）的遗传原因即MECP2基因突变。MeCP2蛋白质与基因太少造成女孩逐渐失去讲话等许多认知功能。

2005年，其他研究人员发现硬币的另一面--MECP2复制综合症。这一关键蛋白质太多会导致其他神经系统的问题，主要发生在男性婴儿上，能影响他们的认知和神经系统的发育。然而，这些男孩有另一个令人担忧的问题。他们往往患上毁灭性的感染，往往是肺炎。

在12月5日发表在Science Translational Medicine杂志上的研究报告中，研究人员确定了这些感染的罪魁祸首。同样，研究还证实了过量的MeCP2是危险的。

患有MeCP2复制综合征的儿童和老鼠的免疫系统缺少重要组成部分，细胞因子γ干扰素。 γ-干扰素是免疫系统对抗入侵病毒和细菌的一个重要工具。用患有疾病的人来源的细胞以及小鼠体内的研究显示，两个群体都缺乏型辅助性T细胞（Th1细胞），后者是产生γ干扰素的关键。

他们的实验室研究表明MeCP2能抑制辅助性T细胞γ-干扰素的分泌，导致局部免疫缺陷。
为了证实这一观点，研究人员发现老鼠无法抵御利什曼原虫的感染。然而，他们能够击退黑曲霉真菌感染，其中就涉及到2型辅助性T细胞的免疫反应。
 
Corry指出，有可能一个正常运作免疫系统的缺乏会促发这些婴儿神经性疾病。这项研究中，临床研究和基础研究相结合，利用小鼠模型研究MeCP2患者的免疫反应，发现MECP2启发感染的关键因素。下一步研究人员要积极找出感染这些孩子的病原体，以及如何最好地治疗他们。

doi:10.1126/scitranslmed.3004430
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Overexpression of Methyl-CpG Binding Protein 2 Impairs TH1 Responses.

Tianshu Yang, Melissa B. Ramocki, Jeffrey L. Neul, Wen Lu, Luz Roberts, John Knight, Christopher S. Ward, Huda Y. Zoghbi, Farrah Kheradmand, and David B. Corry.

The DNA binding protein methyl-CpG binding protein 2 (MeCP2) critically influences neuronal and brain function by modulating gene expression, and children with overexpression of the MECP2 gene exhibit postnatal neurological syndromes. We demonstrate that some children with MECP2 duplication also display variable immunological abnormalities that include reductions in memory T and B cells and natural killer cells and immunoglobulin assay responses. Moreover, whereas mice with MeCP2 overexpression were unable to control infection with the intra-macrophage parasite Leishmania major and secrete interferon-γ (IFN-γ) from involved lymph nodes, they were able to control airway fungal infection by Aspergillus niger and mount protective T helper cell type 2 (TH2)–dependent allergic responses. Relative to normal T cells, TH cells from children and mice with MECP2 duplication displayed similar impairments in IFN-γ secretion and TH1 responses that were due to both MeCP2-dependent suppression of IFN-γ transcription and sequestration of the IFN-γ locus as assessed by chromatin immunoprecipitation assay. Thus, overexpressed MeCP2 aberrantly suppresses IFN-γ secretion from TH cells, potentially leading to a partially immunodeficient state. Our findings establish a rational basis for identifying, treating, and preventing infectious complications potentially affecting children with MECP2 duplication.