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- Title
Gut microbiota from B-cellspecific TLR9-deficient NOD mice promote IL-10<sup>+</sup> Breg cells and protect against T1D.
- Authors
Xin Yang; Juan Huang; Jian Peng; Pai Wang; Wong, F. Susan; Ruirui Wang; Dapeng Wang; Li Wen
- Abstract
Introduction: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing b cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune diseases, and B cell-specific TLR9 deficiency delays T1D development. Gutmicrobiota 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 Tlr9fl/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.
- Subjects
REGULATORY B cells; GUT microbiome; TYPE 1 diabetes; B cells; MICE
- Publication
Frontiers in Immunology, 2024, p01
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2024.1413177