The Biology of Autoimmune Response in the Scurfy Mice that Lack the CD4+Foxp3+ Regulatory T-Cells
Open Access
Abstract
Due to a mutation in the Foxp3 transcription factor, Scurfy mice lack regulatory T-cells that maintain self-tolerance of the immune system. They develop multi-organ inflammation (MOI) and die around four weeks old. The affected organs are skin, tail, lungs and liver. In humans, endocrine and gastrointestinal inflammation are also observed, hence the disease is termed IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome. The three week period of fatal MOI offers a useful autoimmune model in which the controls by genetics, T-cell subsets, cytokines, and effector mechanisms could be efficiently investigated. In this report, we will review published work, summarize our recent studies of Scurfy double mutants lacking specific autoimmune-related genes, discuss the cellular and cytokine controls by these genes on MOI, the organ-specificities of the MOI controlled by environments, and the effector mechanisms regulated by specific Th cytokines, including several newly identified control mechanisms for organ-specific autoimmune response.Keywords
This publication has 63 references indexed in Scilit:
- A novel function of IL-2: Chemokine/chemoattractant/retention receptor genes induction in Th subsets for skin and lung inflammationJournal of Autoimmunity, 2012
- Th17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3− and Foxp3+ Regulatory CD4+ T Cells in an Interleukin-10-Dependent MannerImmunity, 2011
- Regulation of multi-organ inflammation in the regulatory T cell-deficient scurfy miceJournal of Biomedical Science, 2009
- Deficiency in regulatory T cells results in development of antimitochondrial antibodies and autoimmune cholangitis #Hepatology, 2009
- Differential mechanisms in the pathogenesis of autoimmune cholangitis versus inflammatory bowel disease in interleukin‐2Rα−/− mice†Hepatology, 2008
- Innate immunity and intestinal microbiota in the development of Type 1 diabetesNature, 2008
- Nonself-Antigens Are the Cognate Specificities of Foxp3+ Regulatory T CellsImmunity, 2007
- Role of CD28 in fatal autoimmune disorder in scurfy miceBlood, 2007
- Large functional repertoire of regulatory T-cell suppressible autoimmune T cells in scurfy miceJournal of Autoimmunity, 2007
- Foxp3 in control of the regulatory T cell lineageNature Immunology, 2007