Nf-kappab2 is Required for the Control of Autoimmunity by Regulating the Development of Medullary Thymic Epithelial Cells.
From: Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3035 Arlington Avenue, Toledo, OH 43614, USA.
The Journal of biological chemistry
- Publish Date: Dec 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 50
- Pages: 38617-24
- Medium: Print
- Language: English
- Citation (JAMA): Zhang Baochun, Wang Zhe, Ding Jane, et al. Nf-kappab2 is Required for the Control of Autoimmunity by Regulating the Development of Medullary Thymic Epithelial Cells.. J. Biol. Chem. Dec 2006;281:38617-24
Abstract
Medullary thymic epithelial cells function as antigen-presenting cells in negative selection of self-reactive T cell clones, a process essential for the establishment of central self-tolerance. These cells mirror peripheral tissues through promiscuous expression of a diverse set of tissue-restricted self-antigens. The genes and signaling pathways that regulate the development of medullary thymic epithelial cells are not fully understood. Here we show that mice deficient in NF-kappaB2, a member of the NF-kappaB family, display a marked reduction in the number of mature medullary thymic epithelial cells that express CD80 and bind the lectin Ulex europaeus agglutinin-1, leading to a significant decrease in the extent of promiscuous gene expression in the thymus of NF-kappaB2(-/-) mice. Moreover, NF-kappaB2(-/-) mice manifest autoimmunity characterized by multiorgan infiltration of activated T cells and high levels of autoantibodies to multiple organs. A subpopulation of the mice also develops immune complex glomerulonephritis. These findings identify a physiological function of NF-kappaB2 in the development of medullary thymic epithelial cells and, thus, the control of self-tolerance induction.
Mesh Headings (Keywords): Animals, Autoimmune Diseases, Epithelial Cells, Fluorescent Antibody Technique, Mice, Mice, Knockout, NF-kappa B, Thymus Gland
Check for Full Text / PubMed Unique Identifier (PMID): 17046818
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