Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse-transcytosis, the apical-to-basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2-microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC-purified IgA, we show that reverse-transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA-bound microbiota in CD and UC showed distinct IgA1- and IgA2-associated microbiota; the IgA1⁺ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti-glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.

中文翻译：

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微生物群抗体介导的免疫选择的改变有助于炎症性肠病的生态失调

人类分泌性免疫球蛋白 (SIg) A1 和 SIgA2 引导粘膜对耐受性或炎症的反应，特别是通过逆向转胞吞作用，即 IgA2 免疫复合物通过肠道派尔斑的 M 细胞从顶端到基底的转运。因此，维持多样化的肠道微生物群需要广泛的亲和力 IgA 和聚糖-聚糖相互作用。在这里，我们询问 IgA1 和 IgA2-微生物群的相互作用是否可能参与炎症性肠病期间的生态失调诱导。使用粪便 HPLC 纯化的 IgA，我们表明反转胞吞作用在溃疡性结肠炎 (UC) 中被消除，而在克罗恩病 (CD) 中它扩展到 IgA1。CD 和 UC 中 IgA 结合微生物群的 16S RNA 测序显示不同的 IgA1 和 IgA2 相关微生物群；IgA1 ⁺CD微生物群的一部分明显富含有益的共生体。这些特征与 CD 中 IgA 抗聚糖反应性增加和 UC 中相反的反应性丧失有关。我们的研究结果突出了 IgA 在 IBD 中可能支持生态失调的先前未知的致病特性。