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神经发育障碍后代胃肠炎症风险增加的机制
作者:小柯机器人 发布时间:2021/12/11 14:03:25

美国哈佛医学院Jun R. Huh和美国麻省理工学院Gloria B. Choi研究组合作取得最新进展。他们发现母体肠道细菌通过改变 CD4+ T 细胞的染色质结构来驱动患有神经发育障碍后代的肠道炎症。这一研究成果于2021年12月7日发表在国际顶尖学术期刊《免疫学》上。

他们表明,由于产前接触母体炎症而表现出自闭症样表型的小鼠后代在以后的生活中更容易发生肠道炎症。与其在神经发育表型中的产前作用相反,白细胞介素 17A (IL-17A) 通过母体肠道微生物群的变化在后代中产生免疫引发表型,这导致先天 CD4+ T 细胞染色质结构的出生后改变。将具有增强的 IL-17A 反应的怀孕小鼠的粪便样本转移到无菌水中,在后代中产生了免疫引发的表型。他们的研究提供了关于为什么在子宫内接触高度炎症的儿童除了神经发育障碍外,患炎症性疾病的风险可能增加的机制见解。

研究人员表示,患有自闭症谱系障碍的儿童经常表现出失调的免疫反应和相关的胃肠道症状。然而,导致这两种表型发展的潜在机制尚未阐明。

附:英文原文

Title: Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells

Author: Eunha Kim, Donggi Paik, Ricardo N. Ramirez, Delaney G. Biggs, Youngjun Park, Ho-Keun Kwon, Gloria B. Choi, Jun R. Huh

Issue&Volume: 2021-12-07

Abstract: Children with autism spectrum disorders often display dysregulated immune responsesand related gastrointestinal symptoms. However, the underlying mechanisms leadingto the development of both phenotypes have not been elucidated. Here, we show thatmouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternalinflammation were more susceptible to developing intestinal inflammation followingchallenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes,interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changesin the maternal gut microbiota that led to postnatal alterations in the chromatinlandscape of naive CD4+ T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responsesinto germ-free dams produced immune-primed phenotypes in offspring. Our study providesmechanistic insights into why children exposed to heightened inflammation in the wombmight have an increased risk of developing inflammatory diseases in addition to neurodevelopmentaldisorders.

DOI: 10.1016/j.immuni.2021.11.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00496-9

 

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx