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Maternal antibiotic exposure enhances ILC2 activation in neonates via downregulation of IFN1 signaling

Author

Listed:
  • Haixu Xu

    (Tianjin Medical University)

  • Xianfu Yi

    (Tianjin Medical University)

  • Zhaohai Cui

    (Tianjin Medical University)

  • Hui Li

    (Tianjin Medical University)

  • Lin Zhu

    (Tianjin Medical University)

  • Lijuan Zhang

    (Tianjin Medical University)

  • JiaLe Chen

    (Tianjin Medical University)

  • Xutong Fan

    (Tianjin Medical University)

  • Pan Zhou

    (Tianjin Medical University)

  • Mulin Jun Li

    (Tianjin Medical University)

  • Ying Yu

    (Tianjin Medical University)

  • Qiang Liu

    (Tianjin Medical University General Hospital)

  • Dandan Huang

    (Tianjin Medical University)

  • Zhi Yao

    (Tianjin Medical University)

  • Jie Zhou

    (Tianjin Medical University
    the Third Affiliated Hospital of Guangzhou Medical University)

Abstract

Microbiota have an important function in shaping and priming neonatal immunity, although the cellular and molecular mechanisms underlying these effects remain obscure. Here we report that prenatal antibiotic exposure causes significant elevation of group 2 innate lymphoid cells (ILC2s) in neonatal lungs, in both cell numbers and functionality. Downregulation of type 1 interferon signaling in ILC2s due to diminished production of microbiota-derived butyrate represents the underlying mechanism. Mice lacking butyrate receptor GPR41 (Gpr41-/-) or type 1 interferon receptor IFNAR1 (Ifnar1-/-) recapitulate the phenotype of neonatal ILC2s upon maternal antibiotic exposure. Furthermore, prenatal antibiotic exposure induces epigenetic changes in ILC2s and has a long-lasting deteriorative effect on allergic airway inflammation in adult offspring. Prenatal supplementation of butyrate ameliorates airway inflammation in adult mice born to antibiotic-exposed dams. These observations demonstrate an essential role for the microbiota in the control of type 2 innate immunity at the neonatal stage, which suggests a therapeutic window for treating asthma in early life.

Suggested Citation

  • Haixu Xu & Xianfu Yi & Zhaohai Cui & Hui Li & Lin Zhu & Lijuan Zhang & JiaLe Chen & Xutong Fan & Pan Zhou & Mulin Jun Li & Ying Yu & Qiang Liu & Dandan Huang & Zhi Yao & Jie Zhou, 2023. "Maternal antibiotic exposure enhances ILC2 activation in neonates via downregulation of IFN1 signaling," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43903-x
    DOI: 10.1038/s41467-023-43903-x
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    References listed on IDEAS

    as
    1. Jakob Stokholm & Martin J. Blaser & Jonathan Thorsen & Morten A. Rasmussen & Johannes Waage & Rebecca K. Vinding & Ann-Marie M. Schoos & Asja Kunøe & Nadia R. Fink & Bo L. Chawes & Klaus Bønnelykke & , 2018. "Publisher Correction: Maturation of the gut microbiome and risk of asthma in childhood," Nature Communications, Nature, vol. 9(1), pages 1-2, December.
    2. Jakob Stokholm & Martin J. Blaser & Jonathan Thorsen & Morten A. Rasmussen & Johannes Waage & Rebecca K. Vinding & Ann-Marie M. Schoos & Asja Kunøe & Nadia R. Fink & Bo L. Chawes & Klaus Bønnelykke & , 2018. "Maturation of the gut microbiome and risk of asthma in childhood," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
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