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IRIS è il sistema di gestione integrata dei dati della ricerca (persone, progetti, pubblicazioni, attività) adottato dall'Università degli Studi di Milano.

AIR nasce in UNIMI nel 2006 con lo scopo di raccogliere, documentare e conservare le informazioni sulla produzione scientifica dell'Università degli Studi di Milano e costituisce di fatto l'Anagrafe della ricerca dell'Ateneo.

Omenn syndrome (OS) is an atypical primary immunodeficiency characterized by severe autoimmunity because of activated T cells infiltrating target organs. The impaired recombinase activity in OS severely affects expression of the pre- T-cell receptor complex in immature thymocytes, which is crucial for an efficient development of the thymic epithelial component. Anti-CD3ε monoclonal antibody (mAb) treatment in RAG2 -/- mice was previously shown to mimic pre-TCR signaling promoting thymic expansion. Here we show the effect of anti-CD3ε mAb administration in the RAG2 R229Q mouse model, which closely recapitulates human OS. These animals, in spite of the inability to induce the autoimmune regulator, displayed a significant amelioration in thymic epithelial compartment and an important reduction of peripheral T-cell activation and tissue infiltration. Furthermore, by injecting a high number of RAG2 R229Q progenitors into RAG2 -/- animals previously conditioned with anti-CD3ε mAb, we detected autoimmune regulator expression together with the absence of peripheral immunopathology. These observations indicate that improving epithelial thymic function might ameliorate the detrimental behavior of the cell-autonomous RAG defect. Our data provide important therapeutic proof of concept for future clinical applications of anti-CD3ε mAb treatment in severe combined immunodeficiency forms characterized by poor thymus function and autoimmunity.

Anti-CD3ε mAb improves thymic architecture and prevents autoimmune manifestations in a mouse model of Omenn syndrome : therapeutic implications / V. Marrella, P.L. Poliani, E. Fontana, A. Casati, V. Maina, B. Cassani, F. Ficara, M. Cominelli, F. Schena, M. Paulis, E. Traggiai, P. Vezzoni, F. Grassi, A. Villa. - In: BLOOD. - ISSN 0006-4971. - 120:5(2012 Aug), pp. 1005-1014.

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