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

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2025-04-15 DOI:10.1038/s41467-025-57288-6

Yijun Li, Zhaozhong Zhu, Carlos A. Camargo, Janice A. Espinola, Kohei Hasegawa, Liming Liang

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Abstract

Infants with severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) face increased risks of respiratory diseases in childhood. We conduct epigenome-wide association studies in a multi-ethnic cohort of these infants. We identify 61 differentially methylated regions in infant blood (<1 year of age) associated with recurrent wheezing by age 3 (170 cases, 318 non-cases) and/or asthma by age 6 (112 cases, 394 non-cases). These differentially methylated regions are enriched in the enhancers of peripheral blood neutrophils. Several differentially methylated regions exhibit interaction with rhinovirus infection and/or specific blood cell types. In the same blood samples, circulating levels of 104 proteins correlate with the differentially methylated regions, and many proteins show phenotypic association with asthma. Through Mendelian randomization, we find causal evidence supporting a protective role of higher plasma ST2 (also known as IL1RL1) protein against asthma. DNA methylation is also associated with ST2 protein level in infant blood. Taken together, our findings suggest the contribution of DNA methylation to asthma development through regulating early-life systemic immune responses.

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表观基因组学和蛋白质组学分析为婴儿早期免疫调节和哮喘发展提供了见解

患有严重毛细支气管炎（即需要住院治疗的毛细支气管炎）的婴儿在儿童期患呼吸道疾病的风险增加。我们在这些婴儿的多种族队列中进行了全表观基因组关联研究。我们在婴儿血液（1岁）中鉴定出61个不同的甲基化区域，这些区域与3岁时反复发作的喘息（170例，318例非病例）和/或6岁时的哮喘（112例，394例非病例）相关。这些差异甲基化区域在外周血中性粒细胞增强子中富集。一些差异甲基化区域表现出与鼻病毒感染和/或特定血细胞类型的相互作用。在相同的血液样本中，104种蛋白质的循环水平与差异甲基化区域相关，许多蛋白质显示出与哮喘的表型关联。通过孟德尔随机化，我们发现因果证据支持高血浆ST2（也称为IL1RL1）蛋白对哮喘的保护作用。DNA甲基化也与婴儿血液中ST2蛋白水平有关。综上所述，我们的研究结果表明DNA甲基化通过调节早期全身免疫反应对哮喘发展的贡献。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.