Itchy mice: the identification of a new pathway for the development of autoimmunity

Current Topics in Microbiology and Immunology
Lydia E MatesicNancy Jenkins

Abstract

Itchy mice possess a loss-of-function mutation in a HECT-domain-containing ubiquitin ligase (E3), Itch. Homozygous itchy mice develop a systemic and progressive autoimmune disease that proves lethal beginning at 6 months of age. Numerous targets of Itch-mediated ubiquitination have been identified, and some of these have defined physiological roles for Itch signaling in Tcell anergy and T cell differentiation. Studies of itchy mice have also allowed for the identification of a novel pathway involved in autoimmunity: noncanonical Notch signaling. In itchy mice carrying an activated Notch1 transgene, there are increased amounts of full-length Notch1, which can complex with p56(lck) and PI3K to activate a cell survival signal that is mediated by phospho-AKT. This, in turn, leads to a reduction in apoptosis in the thymus and may have consequences in T cell tolerance. A role for noncanonical Notch signaling in autoimmune disease is also supported by numerous mouse knockout studies, and suggests possible new therapeutic approaches for the treatment of autoimmune disease.

Citations

Oct 31, 2015·Experimental Biology and Medicine·Angela R StermerJohn H Richburg
Jul 12, 2020·European Journal of Immunology·Ying FangRenxi Wang
Oct 11, 2011·Cellular and Molecular Life Sciences : CMLS·Eleonora Gambineri, Troy R Torgerson
Mar 23, 2012·Immunological Reviews·Edward W Harhaj, Vishva M Dixit
Sep 3, 2011·Immunological Reviews·Matthew T Sorbara, Dana J Philpott
Jan 7, 2016·Frontiers in Immunology·Claire E O'LearyPaula M Oliver
Jun 7, 2012·Spermatogenesis·Jessica L Dwyer, John H Richburg
Dec 8, 2017·The Journal of Biological Chemistry·Jessica M PerezDerek W Abbott
Feb 9, 2016·Biochemistry·Nathaniel C NoyesDudley K Strickland

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis