An inhibitory immunoreceptor Allergin-1 regulates the intestinal dysbiosis and barrier function in mice.

IF 4.8 4区 医学 Q2 IMMUNOLOGY
Yu-Hsien Lin, Satoko Tahara-Hanaoka, Nozomu Obana, Shinji Fukuda, Akira Shibuya
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Abstract

The intestinal barrier consists of mucosal, epithelial, and immunological barriers and serves as a dynamic interface between the host and its environment. Disruption of the intestinal barrier integrity is a leading cause of various gastrointestinal diseases, such as inflammatory bowel disease. The homeostasis of the intestinal barrier is tightly regulated by crosstalk between gut microbes and the immune system; however, the implication of the immune system on the imbalance of gut microbes that disrupts barrier integrity remains to be fully elucidated. An inhibitory immunoglobulin-like receptor, Allergin-1, is expressed on mast cells and dendritic cells and inhibits Toll-like receptor (TLR)-2 and TLR-4 signaling in these cells. Since TLRs are major sensors of microbiota and are involved in local epithelial homeostasis, we investigated the role of Allergin-1 in maintaining intestinal homeostasis. Allergin-1-deficient (Milr1-/-) mice exhibited more severe dextran sulfate sodium (DSS)-induced colitis than did wild-type (WT) mice. Milr1-/- mice showed an enhanced intestinal permeability compared with WT mice even before DSS administration. Treatment of Milr1-/- mice with neomycin, but not ampicillin, restored intestinal barrier integrity. The 16S rRNA gene sequencing analysis demonstrated that Bifidobacterium pseudolongum was the dominant bacterium in Milr1-/- mice after treatment with ampicillin. Although the transfer of B. pseudolongum to germ-free WT mice had no effect on intestinal permeability, its transfer into ampicillin-treated WT mice enhanced intestinal permeability. These results demonstrated that Allergin-1 deficiency enhanced intestinal dysbiosis with expanded B. pseudolongum, which contributes to intestinal barrier dysfunction in collaboration with neomycin-sensitive and ampicillin-resistant microbiota.

抑制性免疫受体 Allergin-1 调节小鼠肠道菌群失调和屏障功能。
肠道屏障由粘膜、上皮和免疫屏障组成,是宿主与其环境之间的动态界面。肠屏障完整性的破坏是导致炎症性肠病等各种胃肠道疾病的主要原因。肠道屏障的平衡受到肠道微生物和免疫系统之间相互影响的密切调节;然而,免疫系统对肠道微生物失衡破坏屏障完整性的影响仍有待全面阐明。一种抑制性免疫球蛋白样受体 Allergin-1 在肥大细胞和树突状细胞上表达,可抑制这些细胞中的 Toll 样受体(TLR)-2 和 TLR-4 信号传导。由于 TLR 是微生物群的主要传感器并参与局部上皮细胞的平衡,我们研究了 Allergin-1 在维持肠道平衡中的作用。与野生型(WT)小鼠相比,Allergin-1缺陷型(Milr1-/-)小鼠表现出更严重的葡聚糖硫酸钠(DSS)诱导的结肠炎。即使在服用右旋糖酐硫酸钠之前,Milr1-/-小鼠的肠道通透性也比 WT 小鼠强。用新霉素(而非氨苄青霉素)治疗 Milr1-/- 小鼠可恢复肠道屏障的完整性。16S rRNA 基因测序分析表明,在使用氨苄青霉素治疗后,假长双歧杆菌是 Milr1-/- 小鼠体内的优势细菌。虽然将假龙双歧杆菌转入无菌的 WT 小鼠体内对肠道通透性没有影响,但将其转入氨苄青霉素处理过的 WT 小鼠体内会增强肠道通透性。这些结果表明,Allergin-1 缺乏会增强肠道菌群失调,假龙胆(B. pseudolongum)扩大,与新霉素敏感和氨苄西林耐药微生物群共同导致肠道屏障功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International immunology
International immunology 医学-免疫学
CiteScore
9.30
自引率
2.30%
发文量
51
审稿时长
6-12 weeks
期刊介绍: International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.
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