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.
Keyphrases
- pregnant women
- early life
- nk cells
- dendritic cells
- cell proliferation
- signaling pathway
- birth weight
- dna methylation
- stem cells
- single cell
- fatty acid
- gestational age
- cell cycle arrest
- bone marrow
- high fat diet
- metabolic syndrome
- weight loss
- adipose tissue
- body mass index
- allergic rhinitis
- physical activity
- skeletal muscle
- cystic fibrosis
- cell death
- weight gain