Mutations in X-linked gene methyl-CpG-binding protein 2 (MECP2), a key transcriptional regulator, account for most cases of Rett syndrome (RTT), a devastating neurodevelopmental disorder with no known cure. Despite extensive research to elucidate MeCP2 functions, the mechanisms underlying RTT pathophysiology are still unclear. In addition to a variety of neurological symptoms, RTT also includes a plethora of additional phenotypical features including altered lipid metabolism, redox imbalance, immune dysfunction and mitochondrial abnormalities that explain its multisystemic nature. Here, we provide an overview of the current knowledge on the potential role of dysregulated inflammatory and immune responses in RTT. The findings show that abnormalities of humoral and cell-mediated immunity together with chronic low-grade inflammation in multiple organs represent not only clinical manifestations of RTT but rather can contribute to its development and deteriorating course. A future research challenge could be to target therapeutically immune dysfunction as a novel means for RTT management.

中文翻译：

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Rett综合征的免疫/炎症反应受损。

X连锁基因甲基CpG结合蛋白2（MECP2）的突变是关键的转录调节因子，可导致大多数瑞特综合征（RTT）病例，这是一种破坏性的神经发育障碍，尚无治愈方法。尽管进行了广泛的研究以阐明MeCP2功能，但RTT病理生理学的基础机制仍不清楚。除了多种神经系统症状外，RTT还包括许多其他表型特征，包括脂代谢改变，氧化还原失衡，免疫功能障碍和线粒体异常，这可以解释其多系统性。在这里，我们提供了有关RTT中炎症和免疫反应失调的潜在作用的最新知识的概述。这些发现表明，体液和细胞介导的免疫异常以及多个器官中的慢性低度炎症不仅代表RTT的临床表现，而且可以促进RTT的发展和病程恶化。未来的研究挑战可能是将治疗性免疫功能障碍作为RTT管理的新手段。