Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells
Name
nihms-1758296.pdf
Description
Accepted version
Size
2.3 MB
Format
Adobe PDF
Checksum (MD5)
07b3009225bb85a83d96efc2bf9d2af3
Author(s)
Kim, Eunha
Paik, Donggi
Ramirez, Ricardo N
Biggs, Delaney G
Park, Youngjun
Kwon, Ho-Keun
Choi, Gloria B
Huh, Jun R
Date Issued
2022
Journal
Immunity
Publisher
Elsevier BV
Citation
Kim, Eunha, Paik, Donggi, Ramirez, Ricardo N, Biggs, Delaney G, Park, Youngjun et al. 2022. "Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells." Immunity, 55 (1).
Version
Author's final manuscript
Abstract
Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms. However, the underlying mechanisms leading to the development of both phenotypes have not been elucidated. Here, we show that mouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternal inflammation were more susceptible to developing intestinal inflammation following challenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes, interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changes in the maternal gut microbiota that led to postnatal alterations in the chromatin landscape of naive CD4+ T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responses into germ-free dams produced immune-primed phenotypes in offspring. Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.IMMUNI.2021.11.005
