Cbl-b and Itch: Key Regulators of Peripheral T-cell Tolerance

E3 ligases Cbl-b and Itch have emerged as dominant tolerogenic regulators of T cells because their deficiency results in severe autoimmune diseases. Cbl-b and Itch ligase activity regulate T-cell anergy and development of Foxp3+ regulatory T cells (Treg) in the periphery by modulating key components of T-cell receptor (TCR) and transforming growth factor-beta (TGF-beta) signaling. Manipulation of Cbl-b and Itch activities may provide unique opportunities to develop future therapies for immune disorders such as autoimmunity and cancer. Cancer Res; 70(8); 3009-12. (C) 2010 AACR.