Alajoleen, Razan Mefleh Tayi2023-12-052023-12-052023-12-04vt_gsexam:38888https://hdl.handle.net/10919/116737Systemic Lupus Erythematosus (SLE) stands as a multifaceted autoimmune disorder, characterized by a spectrum of clinical manifestations and the generation of autoantibodies against self-antigens. Our focus was on the pivotal role of B cells in the development of SLE. The study also underscored the significant contribution of regulatory B (Breg) cells in the context of SLE, suggesting their potential as key regulators of the disease process. Our results provided a deeper understanding of the intricate interplay between B cells and SLE, offering insights that were valuable for both scientific research and future designs of therapeutic approaches. Cutting-edge single-cell RNA sequencing was employed to analyze the differences in splenic Breg subsets and their molecular profiles across different stages of lupus development in mice. Transcriptome-based changes in Bregs during active disease were confirmed through phenotypic analysis. These findings provided crucial insights into the dynamic role of B cells in the pathogenesis of SLE. In addition, we delved into the intricate connection between SLE and the gut microbiota. A literature review offered a comprehensive analysis of current research, with a particular emphasis on potential interactions between bacterial flagellin and Toll-Like Receptor 5 (TLR5) on immune cells. These interactions garnered substantial attention due to their potential implications in the pathogenesis of SLE. We synthesized existing research, providing valuable insights into the complex interplay between SLE and the microbiota and suggesting promising avenues for further investigation and potential therapeutic interventions. In the final study, we explored lupus-like disease in mice with global Tlr5 deletion, initially expecting disease attenuation. Surprisingly, the results revealed an exacerbation of lupus-like symptoms, particularly in female mice lacking Tlr5. Future research will seek to uncover the mechanisms by which Tlr5 deletion modulates interactions between the host and the gut microbiota, ultimately contributing to the exacerbation of lupus-like disease.ETDenIn CopyrightSLEBreg cellsIl-10Tlr5Gut microbiomeDissertation