ITCH E3 ubiquitin ligase deficiency D81.4

Since the discovery of ITCH in 1998, hundreds of publications have described mechanisms by which Itch controls various biological activities in immune and non-immune cells. Other studies have shed light on how the catalytic activity of Itch is regulated. Although autoimmunity is the primary clinical feature that occurs in both mice and humans lacking Itch, and the control of immune cell function by ITCH has been well studied, it remains unclear how ITCH prevents the onset of autoimmune diseases.

Very rare is a rare, genetic (mutations in the ITCH gene), systemic autoimmune disorder characterized by the following clinical symptoms: Failure to thrive, global developmental delay, marked craniofacial dysmorphism (relative macrocephaly, dolichocephaly, frontal hump, orbital proptosis, flattened midface with protruding occiput, low, posteriorly rotated ears, micrognathia), hepatomegaly and/or splenomegaly, and multisystemic autoimmune disease involving the lungs, liver, intestines, and/or thyroid.

ITCH is a HECT-type E3 ubiquitin ligase that is required to prevent the development of autoimmune diseases in humans. ITCH is expressed in most mammalian cell types and regulates many cellular signaling pathways, from T-cell differentiation to liver tumorigenesis, according to published data (Moser EK et al. 2019).

1. Moser EK et al (2019) Regulation of autoimmune disease by the E3 ubiquitin ligase Itch. Cell Immunol 340:103916.
2. Wang A et al. (2019) Regulation of T cell differentiation and function by ubiquitin-specific proteases. Cell Immunol 340:103922.