Abstract
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.
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