Maternal OM-85 administration alleviates offspring allergic airway inflammation by downregulating IL-33/ILC2 axis.

IF 4.3 2区医学 Q2 ALLERGY

Pediatric Allergy and Immunology Pub Date : 2025-02-01 DOI:10.1111/pai.70044

Wei Zou, Donghai Ma, Fengfei Sun, Zehu Chen, Ying Chen, Xuegang Li, Meizhu Chen, Minmin Lin, Honglei Shi, Baihe Wu, Lei Chen, Zibin Liang, Jing Liu

{"title":"Maternal OM-85 administration alleviates offspring allergic airway inflammation by downregulating IL-33/ILC2 axis.","authors":"Wei Zou, Donghai Ma, Fengfei Sun, Zehu Chen, Ying Chen, Xuegang Li, Meizhu Chen, Minmin Lin, Honglei Shi, Baihe Wu, Lei Chen, Zibin Liang, Jing Liu","doi":"10.1111/pai.70044","DOIUrl":null,"url":null,"abstract":"Background: Type 2 innate lymphoid cells (ILC2s) are essential for maintaining immune regulation and promoting tissue homeostasis in allergic asthma. How the development of gut microbiota on neonatal ILC2s influences allergic airway inflammation remains unclear. Here we focus on offspring ILC2 development in the context of alterations in maternal gut microbiota.Methods: C57BL/6 maternal mice were gavaged with OM-85 during pregnancy and/or lactation, ILC2-driven allergic airway inflammation in the OVA-sensitized adult offspring was observed. ILC2 development in offspring early life were investigated using recombinant (r)IL-33, rIL-25 and Bromodeoxyuridine in the vivo experiments. Further ILC2 promoting factors- IL-33 and IL-25 production in offspring early life were analysed. Finally, we examined the changes in gut microbiota and its metabolites in both dams and pups, and explored the effects of short-chain fatty acids (SCFAs) on IL-33 expression and secretion.Results: Maternal OM-85 administration restrained ILC2-driven allergic airway inflammation in the OVA-sensitized adult offspring. During ILC2 development in offspring early life, maternal OM-85 administration suppressed IL-33 and IL-25 production to inhibit ILC2 expansion and ILC2 responsiveness to alarmins, and infantile ILC2s could persist into adulthood. Maternal OM-85 administration increased SCFAs in breast milk and SCFA-producing gut probiotics (predominant Bacteroides and Blautia) in offspring, especially during pregnancy and lactation. SCFAs down-regulated IL-33 expression and reduced IL-33 secretion by inhibited gasdermin D (GSDMD) formation.Conclusion: Maternal OM-85 administration restrains ILC2-driven allergic airway inflammation in adult offspring by increasing offspring intestinal SCFAs to modulate ILC2 development at an early stage, demonstrating that the transgenerational effects of maternal OM-85 exposure on offspring innate immunity.","PeriodicalId":19929,"journal":{"name":"Pediatric Allergy and Immunology","volume":"36 2","pages":"e70044"},"PeriodicalIF":4.3000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Allergy and Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/pai.70044","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Type 2 innate lymphoid cells (ILC2s) are essential for maintaining immune regulation and promoting tissue homeostasis in allergic asthma. How the development of gut microbiota on neonatal ILC2s influences allergic airway inflammation remains unclear. Here we focus on offspring ILC2 development in the context of alterations in maternal gut microbiota.

Methods: C57BL/6 maternal mice were gavaged with OM-85 during pregnancy and/or lactation, ILC2-driven allergic airway inflammation in the OVA-sensitized adult offspring was observed. ILC2 development in offspring early life were investigated using recombinant (r)IL-33, rIL-25 and Bromodeoxyuridine in the vivo experiments. Further ILC2 promoting factors- IL-33 and IL-25 production in offspring early life were analysed. Finally, we examined the changes in gut microbiota and its metabolites in both dams and pups, and explored the effects of short-chain fatty acids (SCFAs) on IL-33 expression and secretion.

Results: Maternal OM-85 administration restrained ILC2-driven allergic airway inflammation in the OVA-sensitized adult offspring. During ILC2 development in offspring early life, maternal OM-85 administration suppressed IL-33 and IL-25 production to inhibit ILC2 expansion and ILC2 responsiveness to alarmins, and infantile ILC2s could persist into adulthood. Maternal OM-85 administration increased SCFAs in breast milk and SCFA-producing gut probiotics (predominant Bacteroides and Blautia) in offspring, especially during pregnancy and lactation. SCFAs down-regulated IL-33 expression and reduced IL-33 secretion by inhibited gasdermin D (GSDMD) formation.

Conclusion: Maternal OM-85 administration restrains ILC2-driven allergic airway inflammation in adult offspring by increasing offspring intestinal SCFAs to modulate ILC2 development at an early stage, demonstrating that the transgenerational effects of maternal OM-85 exposure on offspring innate immunity.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Pediatric Allergy and Immunology 医学-过敏

CiteScore

9.10

自引率

9.10%

发文量

200

审稿时长

4-8 weeks

期刊介绍： Pediatric Allergy and Immunology is the world''s leading journal in pediatric allergy, publishing original contributions and comprehensive reviews related to the understanding and treatment of immune deficiency and allergic inflammatory and infectious diseases in children. Other areas of interest include: development of specific and accessory immunity; the immunological interaction during pregnancy and lactation between mother and child. As Pediatric Allergy and Immunology promotes communication between scientists engaged in basic research and clinicians working with children, we publish both clinical and experimental work.