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Epigenomic and proteomic analyses provide insights into early-life immune regulation and asthma development in

Yijun Li1, Zhaozhong Zhu2, Carlos A Camargo2

  • 1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Nature Communications
|April 14, 2025
PubMed

Insights

Severe bronchiolitis in infants increases childhood respiratory risks. DNA methylation in infant blood is linked to later wheezing and asthma, potentially through immune responses. This study identifies key epigenetic markers and proteins like ST2.

Area of Science:

  • Epigenetics
  • Immunology
  • Pediatric Respiratory Medicine

Background:

  • Infants hospitalized for severe bronchiolitis have a higher risk of developing childhood respiratory diseases.
  • Early-life respiratory infections can have long-term consequences on lung health.

Purpose of the Study:

  • To investigate the role of DNA methylation in infants with severe bronchiolitis.
  • To identify epigenetic markers associated with recurrent wheezing and asthma development by age 6.
  • To explore the relationship between DNA methylation, protein levels, and asthma risk.

Main Methods:

  • Epigenome-wide association studies (EWAS) were performed on infant blood samples.
  • Differentially methylated regions (DMRs) were identified and analyzed for associations with wheezing and asthma.
  • Correlation analyses were conducted between DMRs and circulating protein levels.
  • Mendelian randomization was used to assess the causal effect of ST2 protein on asthma.

Main Results:

  • 61 DMRs were associated with recurrent wheezing and/or asthma.
  • These DMRs were enriched in neutrophil enhancers and showed interactions with rhinovirus infection.
  • Circulating levels of 104 proteins correlated with DMRs, with many linked to asthma phenotypes.
  • Higher plasma ST2 (IL1RL1) protein levels showed a protective causal effect against asthma.

Conclusions:

  • DNA methylation contributes to asthma development by regulating early-life systemic immune responses.
  • Epigenetic modifications in infancy may serve as biomarkers for future respiratory disease risk.
  • ST2 protein plays a protective role in asthma development, influenced by DNA methylation.

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