Maternal Antibiotic Exposure Enhances ILC2 Activation in Neonates Via Downregulation of IFN1 Signaling

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Dec 14

PMID 38097561

Authors

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

Affiliations

Soon will be listed here.

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.

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