| First Author | Yang X | Year | 2024 |
| Journal | Front Immunol | Volume | 15 |
| Pages | 1413177 | PubMed ID | 38903498 |
| Mgi Jnum | J:360319 | Mgi Id | MGI:7659490 |
| Doi | 10.3389/fimmu.2024.1413177 | Citation | Yang X, et al. (2024) Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10(+) Breg cells and protect against T1D. Front Immunol 15:1413177 |
| abstractText | INTRODUCTION: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing beta 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
