Dissection of Cellular and Molecular Mechanisms Underlying Autoimmunity in Omenn Syndrome

Omenn syndrome (OS) is a severe immunodeficiency characterized by severe infections associated with the presence of activated T cells which infiltrate skin and gut causing severe erythrodermia and chronic diarrhea. Patients die early in life if not cured by hematopoietic stem cell transplantation. In the past, our group identified Rag1 and Rag2 as the genes responsible for the disease. Although the identification of the molecular bases has allowed the precise diagnosis of the disease, many aspects of the disease still remain enigmatic. Thanks to availability of a mouse model, recently generated in our laboratory and well recapitalizing the disease, we aim at carefully studying the cellular and molecular bases of autoimmunity observed in OS patients. To this end, we will study in detail the mechanisms controlling the generation of autoreactive cells and the role played by viral infections in the pathogenesis of the disease. Results obtained from this study will be important not only for the elucidation of the pathophysiology of the disease, but also for the clinical management of the patients.