免疫学
自身免疫
FOXP3型
免疫系统
CD19
自身抗体
周边公差
医学
生物
抗体
作者
Matteo Doglio,Alessio Ugolini,Clara Bercher-Brayer,Barbara Camisa,T. Constantin,Rossana Norata,Stefano Rosso,Raffaella Greco,Fabio Ciceri,Francesca Sanvito,Monica Casucci,Angelo A. Manfredi,Chiara Bonini
标识
DOI:10.1038/s41467-024-46448-9
摘要
Abstract Systemic Lupus Erythematosus (SLE) is a progressive disease leading to immune-mediated tissue damage, associated with an alteration of lymphoid organs. Therapeutic strategies involving regulatory T (Treg) lymphocytes, which physiologically quench autoimmunity and support long-term immune tolerance, are considered, as conventional treatment often fails. We describe here a therapeutic strategy based on Tregs overexpressing FoxP3 and harboring anti-CD19 CAR (Fox19CAR-Tregs). Fox19CAR-Tregs efficiently suppress proliferation and activity of B cells in vitro, which are relevant for SLE pathogenesis. In an humanized mouse model of SLE, a single infusion of Fox19CAR-Tregs restricts autoantibody generation, delay lymphopenia (a key feature of SLE) and restore the human immune system composition in lymphoid organs, without detectable toxicity. Although a short survival, SLE target organs appear to be protected. In summary, Fox19CAR-Tregs can break the vicious cycle leading to autoimmunity and persistent tissue damage, representing an efficacious and safe strategy allowing restoration of homeostasis in SLE.
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