■1型糖尿病(T1D)是一种自身免疫性疾病,其特征是破坏产生胰岛素的β细胞。Toll样受体9(TLR9)在自身免疫性疾病中发挥作用,和B细胞特异性TLR9缺乏延迟T1D的发展。肠道菌群与T1D有关,虽然关系很复杂。然而,B细胞特异性TLR9缺乏对肠道菌群的影响以及肠道菌群改变对T1D发生发展的影响尚不清楚.
这项研究调查了肠道微生物群和肠道屏障如何促进B细胞特异性TLR9缺陷型NOD小鼠的T1D发育。此外,本研究探讨了微生物群在免疫调节和T1D发病中的作用。
■这项研究评估了肠道通透性,与肠屏障完整性相关的基因表达,和肠道菌群组成。抗生素耗尽的肠道微生物群,将粪便样品转移至无菌小鼠。该研究还检查了IL-10的产生,Breg细胞分化,以及它们对T1D发展的影响。
■B细胞特异性TLR9缺陷型NOD小鼠表现出肠通透性增加和肠屏障相关基因表达下调。抗生素恢复了肠道通透性,提示微生物群的影响。改变的微生物群富集在落叶松科中,以粘蛋白降解而闻名。将这种微生物群转移到无菌小鼠增加肠道通透性并促进表达IL-10的Breg细胞。用来自Tlr9fl/flCd19-Cre+小鼠的粪便样品移植的rag-/-小鼠显示延迟的糖尿病发作,表明微生物群的影响。
■B细胞特异性TLR9缺乏改变肠道菌群,增加肠道通透性并促进表达IL-10的Breg细胞,延迟T1D。这项研究揭示了TLR9,肠道微生物群之间的联系,和T1D中的免疫调节,对微生物群靶向T1D治疗的影响。
UNASSIGNED: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune diseases, and B cell-specific TLR9 deficiency delays T1D development. Gut microbiota are implicated in T1D, although the relationship is complex. However, the impact of B cell-specific deficiency of TLR9 on intestinal microbiota and the impact of altered intestinal microbiota on the development of T1D are unclear.
UNASSIGNED: This study investigated how gut microbiota and the intestinal barrier contribute to T1D development in B cell-specific TLR9-deficient NOD mice. Additionally, this study explored the role of microbiota in immune regulation and T1D onset.
UNASSIGNED: The study assessed gut permeability, gene expression related to gut barrier integrity, and gut microbiota composition. Antibiotics depleted gut microbiota, and fecal samples were transferred to germ-free mice. The study also examined IL-10 production, Breg cell differentiation, and their impact on T1D development.
UNASSIGNED: B cell-specific TLR9-deficient NOD mice exhibited increased gut permeability and downregulated gut barrier-related gene expression. Antibiotics restored gut permeability, suggesting microbiota influence. Altered microbiota were enriched in Lachnospiraceae, known for mucin degradation. Transferring this microbiota to germ-free mice increased gut permeability and promoted IL-10-expressing Breg cells. Rag-/- mice transplanted with fecal samples from Tlr9 fl/fl Cd19-Cre+ mice showed delayed diabetes onset, indicating microbiota\'s impact.
UNASSIGNED: B cell-specific TLR9 deficiency alters gut microbiota, increasing gut permeability and promoting IL-10-expressing Breg cells, which delay T1D. This study uncovers a link between TLR9, gut microbiota, and immune regulation in T1D, with implications for microbiota-targeted T1D therapies.