Multifaceted role of the ubiquitin ligase Itch in immune regulation

The HECT‐type E3 ligase Itch is increasingly being shown to have a vital role in immune regulation. Itch deficiency leads to deleterious inflammatory disorders both in mice and humans. By adding ubiquitin to the key signaling intermediates, Itch functions as a critical regulator of lymphocyte‐cell activation, differentiation and immune tolerance. Also, Itch cooperates with deubiquitinating enzymes such as A20 and Cyld to terminate NF‐κB signaling and prevent chronic inflammation. This review summarizes recent advances that highlight Itch's role in lymphocyte function and explores recent insights regarding its role as a regulator of inflammatory signaling.