論文

査読有り 国際誌
2022年5月2日

A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model.

Molecular psychiatry
  • Chia-Wen Lin
  • Dian E Septyaningtrias
  • Hsu-Wen Chao
  • Mikiko Konda
  • Koji Atarashi
  • Kozue Takeshita
  • Kota Tamada
  • Jun Nomura
  • Yohei Sasagawa
  • Kaori Tanaka
  • Itoshi Nikaido
  • Kenya Honda
  • Thomas J McHugh
  • Toru Takumi
  • 全て表示

27
8
開始ページ
3343
終了ページ
3354
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41380-022-01566-y

Immune dysregulation plays a key role in the pathogenesis of autism. Changes occurring at the systemic level, from brain inflammation to disturbed innate/adaptive immune in the periphery, are frequently observed in patients with autism; however, the intrinsic mechanisms behind them remain elusive. We hypothesize a common etiology may lie in progenitors of different types underlying widespread immune dysregulation. By single-cell RNA sequencing (sc-RNA seq), we trace the developmental origins of immune dysregulation in a mouse model of idiopathic autism. It is found that both in aorta-gonad-mesonephros (AGM) and yolk sac (YS) progenitors, the dysregulation of HDAC1-mediated epigenetic machinery alters definitive hematopoiesis during embryogenesis and downregulates the expression of the AP-1 complex for microglia development. Subsequently, these changes result in the dysregulation of the immune system, leading to gut dysbiosis and hyperactive microglia in the brain. We further confirm that dysregulated immune profiles are associated with specific microbiota composition, which may serve as a biomarker to identify autism of immune-dysregulated subtypes. Our findings elucidate a shared mechanism for the origin of immune dysregulation from the brain to the gut in autism and provide new insight to dissecting the heterogeneity of autism, as well as the therapeutic potential of targeting immune-dysregulated autism subtypes.

リンク情報
DOI
https://doi.org/10.1038/s41380-022-01566-y
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35491410
ID情報
  • DOI : 10.1038/s41380-022-01566-y
  • PubMed ID : 35491410

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