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

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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.

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母体OM-85通过下调IL-33/ILC2轴减轻子代变应性气道炎症。

背景：2型先天淋巴样细胞（ILC2s）对维持过敏性哮喘的免疫调节和促进组织稳态至关重要。新生儿ILC2s肠道菌群的发育如何影响变应性气道炎症尚不清楚。在这里，我们关注的是在母体肠道微生物群改变的背景下，后代ILC2的发育。方法：在妊娠期和/或哺乳期给C57BL/6母鼠灌胃OM-85，观察ova致敏的成年子代ilc2驱动的变应性气道炎症。利用重组(r)IL-33、il -25和溴脱氧尿苷对子代早期ILC2发育进行体内实验研究。进一步分析后代早期ILC2促进因子IL-33和IL-25的产生。最后，我们检测了公鼠和幼鼠肠道菌群及其代谢物的变化，并探讨了短链脂肪酸（SCFAs）对IL-33表达和分泌的影响。结果：母亲OM-85给药抑制了ova致敏的成年后代ilc2驱动的变应性气道炎症。在后代早期ILC2发育过程中，母体OM-85可抑制IL-33和IL-25的产生，从而抑制ILC2的扩张和ILC2对警报器的反应，婴儿ILC2s可持续到成年。母体给药OM-85增加了母乳中的短链脂肪酸和子代产生短链脂肪酸的肠道益生菌（主要是拟杆菌和蓝杆菌），特别是在怀孕和哺乳期间。SCFAs通过抑制gasdermin D （GSDMD）的形成下调IL-33的表达并减少IL-33的分泌。结论：母体OM-85通过增加后代肠道SCFAs来调节早期ILC2的发育，从而抑制成年后代ILC2驱动的过敏性气道炎症，表明母体OM-85暴露对后代先天免疫的跨代影响。

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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.