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Abstract：
Peyer\'s patches (PPs) are specialized gut-associated lymphoid tissues that initiate follicular helper T (Tfh)-mediated immunoglobulin A (IgA) response to luminal antigens derived from commensal symbionts, pathobionts, and dietary sources. IgA-producing B cells migrate from PPs to the small intestinal lamina propria and secrete IgA across the epithelium, modulating the ecological balance of the commensal microbiota and neutralizing pathogenic microorganisms. α-glucosidase inhibitors (α-GIs) are antidiabetic drugs that inhibit carbohydrate digestion in the small intestinal epithelium, leading to alterations in the commensal microbiota composition and metabolic activity. The commensal microbiota and IgA responses exhibit bidirectional interactions that modulate intestinal homeostasis and immunity. However, the effect of α-GIs on the intestinal IgA response remains unclear. We investigated whether α-GIs affect IgA responses by administering voglibose and acarbose to mice via drinking water. We analyzed Tfh cells, germinal center (GC) B cells, and IgA-producing B cells in PPs by flow cytometry. We also assessed pathogen-specific IgA responses. We discovered that voglibose and acarbose induced Tfh cells, GCB cells, and IgA-producing B cells in the PPs of the proximal small intestine in mice. This effect was attributed to the modification of the microbiota rather than a shortage of monosaccharides. Furthermore, voglibose enhanced secretory IgA (S-IgA) production against attenuated Salmonella Typhimurium. Our findings reveal a novel mechanism by which α-GIs augment antigen-specific IgA responses by stimulating Tfh-GCB responses in PPs, and suggest a potential therapeutic application as an adjuvant for augmenting mucosal vaccines.
摘要：
派尔斑块（PPs）是专门的肠道相关淋巴组织，可启动滤泡辅助性T（Tfh）介导的免疫球蛋白A（IgA）对来自共生共生体的腔内抗原的反应，pathobionts,和饮食来源。产生IgA的B细胞从PPs迁移到小肠固有层，并通过上皮分泌IgA，调节共生微生物的生态平衡和中和病原微生物。α-葡萄糖苷酶抑制剂（α-GI）是抑制小肠上皮中碳水化合物消化的抗糖尿病药物，导致共生微生物群组成和代谢活动的改变。共生微生物群和IgA反应表现出双向相互作用，可调节肠道稳态和免疫力。然而,α-GI对肠道IgA反应的影响尚不清楚。我们通过饮用水向小鼠施用伏格列波糖和阿卡波糖研究了α-GI是否影响IgA反应。我们分析了Tfh细胞，生发中心（GC）B细胞，和通过流式细胞术在PPs中产生IgA的B细胞。我们还评估了病原体特异性IgA应答。我们发现伏格列波糖和阿卡波糖诱导Tfh细胞，GCB细胞,和小鼠近端小肠PPs中产生IgA的B细胞。这种作用归因于微生物群的改变，而不是单糖的短缺。此外，伏格列波糖增强了针对减毒鼠伤寒沙门氏菌的分泌型IgA（S-IgA）生产。我们的发现揭示了一种新的机制，通过这种机制，α-GI通过刺激PPs中的Tfh-GCB反应来增强抗原特异性IgA反应，并提出了作为增强粘膜疫苗的佐剂的潜在治疗应用。
