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Am J Clin Exp Immunol 2012;1(2):101-112
Review Article
The role of ubiquitin ligases in the control of organ specific autoimmunity
Gerard F Hoyne
The School of Health Sciences, University of Notre Dame Australia, Fremantle, Western Australia 6959
Received August 6, 2012; Accepted September 12, 2012; Epub September 27, 2012; Published November 30, 2012
Abstract: Diabetes mellitus is characterized by chronic hyperglycemia caused by a deficiency in insulin action, insulin
secretion or both. Type 1 diabetes is classified as the destruction of beta cells leading to a deficiency in insulin
production. Type1 diabetes accounts for 5-10% of patients with diabetes and most commonly is caused by the
autoimmune destruction of the beta cells in the pancreas. The adaptive immune system is composed of antigen
specific T and B lymphocytes which play a central role in protecting the human body from infectious pathogens but
occasionally autoreactive T and B cells can escape immune tolerance, become activated and induce autoimmune
diseases. Naïve T cells require two distinct signals one delivered via the antigen receptor and the second through
the costimulatory receptor CD28 that leads to the induction of IL-2 gene transcription. IL-2 is an important T cell
growth factor that can influence both immunity and tolerance. Given its pivotal role it is not surprising that the
immune system places strict regulation over Il2 gene transcription that is controlled by a number of E3 ubiquitin
ligases that modulate TCR and CD28 signaling. This review will examine how different E3 ligases function to control
T effector cell differentiation and how studies in gene knockout animal models has been crucial in understanding
how these proteins function in vivo to regulate immune tolerance in the peripheral circulation. (AJCEI1208001).
Keywords: T cells, anergy, Foxp 3, TCR signalling, ubiquitin ligases
Address all correspondence to:
Gerard F Hoyne, School of Health Sciences
University of Notre Dame Australia
19 Mouat St Fremantle, Western Australia 6959.
Phone: 61-8-94330236; Fax: 61-8-94330210
E-mail: gerard.hoyne@nd.edu.au
Review Article
The role of ubiquitin ligases in the control of organ specific autoimmunity
Gerard F Hoyne
The School of Health Sciences, University of Notre Dame Australia, Fremantle, Western Australia 6959
Received August 6, 2012; Accepted September 12, 2012; Epub September 27, 2012; Published November 30, 2012
Abstract: Diabetes mellitus is characterized by chronic hyperglycemia caused by a deficiency in insulin action, insulin
secretion or both. Type 1 diabetes is classified as the destruction of beta cells leading to a deficiency in insulin
production. Type1 diabetes accounts for 5-10% of patients with diabetes and most commonly is caused by the
autoimmune destruction of the beta cells in the pancreas. The adaptive immune system is composed of antigen
specific T and B lymphocytes which play a central role in protecting the human body from infectious pathogens but
occasionally autoreactive T and B cells can escape immune tolerance, become activated and induce autoimmune
diseases. Naïve T cells require two distinct signals one delivered via the antigen receptor and the second through
the costimulatory receptor CD28 that leads to the induction of IL-2 gene transcription. IL-2 is an important T cell
growth factor that can influence both immunity and tolerance. Given its pivotal role it is not surprising that the
immune system places strict regulation over Il2 gene transcription that is controlled by a number of E3 ubiquitin
ligases that modulate TCR and CD28 signaling. This review will examine how different E3 ligases function to control
T effector cell differentiation and how studies in gene knockout animal models has been crucial in understanding
how these proteins function in vivo to regulate immune tolerance in the peripheral circulation. (AJCEI1208001).
Keywords: T cells, anergy, Foxp 3, TCR signalling, ubiquitin ligases
Address all correspondence to:
Gerard F Hoyne, School of Health Sciences
University of Notre Dame Australia
19 Mouat St Fremantle, Western Australia 6959.
Phone: 61-8-94330236; Fax: 61-8-94330210
E-mail: gerard.hoyne@nd.edu.au
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