Fatal Autoimmunity Results from the Conditional Deletion of Snai2 and Snai3

The study demonstrated that the transcription factors Snai2 and Snai3 played redundant roles in the development and maintenance of immune tolerance. Mice with germ line deletion of Snai2 and hematopoietic-specific deletion of Snai3 exhibited severe lymphopenia, alopecia, dermatitis, and fatal autoimmunity, characterized by high levels of autoantibodies and death by 30 days. The autoimmune response was linked to a regulatory T cell defect, as transferring wild type regulatory T cells alleviated symptoms. Transplantation of Snai2/Snai3 double deficient bone marrow into Snai2 sufficient Rag2−/− recipients also resulted in autoantibody generation, underscoring the importance of Snai2 and Snai3 in immune cell development and function.