A role of NF-B and the proteasome in autoimmunity

• Authors: T. Hayashi , D. Faustman
• Languages of publication: EN

Abstracts

EN

Type 1 diabetes (also known as insulin-dependent diabetes mellitus or juvenile-onset diabetes) is usually caused by T cell-mediated autoimmunity, with a prediabetic state characterized by the production of autoantibodies specific for proteins expressed by pancreatic beta cells. The non-obese diabetic (NOD) mouse is a spontaneous model of type 1 diabetes with a strong genetic component that maps to the major histocompatibility complex (MHC) region of the genome. A specific proteasome defect has been identified in NOD mouse lymphocytes that results from down-regulation of expression of the proteasome subunit LMP2, which is encoded by a gene in the MHC genomic region. This defect both prevents the proteolytic processing required for the production and activation of the transcription factor nuclear facktor-kappaB (NF-kappaB), which plays important roles in immune and inflammatory responses, as well as increases the susceptibility of the affected cells to apoptosis induced by tumor necrosis factor alpha (TNF-alpha). The proteasome dysfunction is both tissue and developmental stage specific and likely contributes to disease pathogenesis and tissue targeting.

Keywords

EN

APOPTOSIS; DIABETE; NOD MOUSE; PROTEASOME

Discipline

• IMMUNOLOGY: IMMUNOLOGY

• Publisher: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
• Journal: Archivum Immunologiae et Therapiae Experimentalis
• Year: 2000
• Volume: 48
• Issue: 5
• Pages: 353-365

Contributors

author

T. Hayashi

author

D. Faustman

• Document Type: REVIEW
• Publication order reference: T. Hayashi, Immunobilogy Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA