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M. Doglio, et al.
Nat Commun. 2024.
Imura et al. recently demonstrated the efficacy of naïve-derived anti-CD19 CAR-Tregs in controlling B cell activation and improving Graft-versus-Host Disease (GvHD) in a xenograft mouse model. Fox19CAR-Tregs, expressing both FoxP3 and an anti-CD19 CAR, demonstrated specific immunosuppressive effects against B cells in both in vitro and in vivo settings. The results showed that these engineered Tregs could suppress B cell proliferation effectively in vitro. In a humanized mouse model of SLE, the infusion of Fox19CAR-Tregs led to significant improvements in immune system composition in lymphoid organs and a reduction in autoantibody production, which are critical factors in SLE pathogenesis. The therapy improved the human immune system composition in lymphoid organs without detectable toxicity. The discussion highlights the significance of these findings, noting that engineered Fox19CAR-Tregs not only reduce autoimmune activity but also protect against lymphopenia and organ damage, presenting a potential breakthrough for SLE treatment. These results underscore the therapeutic potential of using antigen-specific Tregs to restore immune balance and prevent chronic tissue damage in autoimmune diseases.
DOI: https://doi.org/10.1038/s41467-024-46448-9
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Signal Transduct Target Ther. 2024.
This study highlights how disruptions in the gut microbiome can exacerbate the severity of a psoriasis-like phenotype. It emphasizes the interaction between the gut microbiota and the host's immune response, particularly the activation of Th17 cells, which are crucial in the development of psoriasis. Experiments using a K14-VEGF transgenic mouse model of psoriasis involving cohabitation and fecal microbiota transplantation (FMT) show that transferring gut microbiota from mice with severe symptoms exacerbates conditions in those with milder symptoms. This includes increased Th17 infiltration and changes in fatty acid metabolism, particularly elevated levels of oleic and stearic acids. The study also evaluates therapeutic interventions such as antibiotics (e.g., gentamicin) and PDE-4 inhibitors, demonstrating their potential to modulate the gut microbiota and alleviate psoriasis symptoms. These findings underscore the potential of targeting the gut microbiota and metabolic pathways as therapeutic strategies for psoriasis.
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