NF-kappa beta 2 is required for the control of autoimmunity by regulating the development of medullary thymic epithelial cells

作者：Zhang Baochun; Wang Zhe; Ding Jane; Peterson Part; Gunning William T; Ding Han Fei^*

来源：Journal of Biological Chemistry, 2006, 281(50): 38617-38624.

DOI：10.1074/jbc.M606705200

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-kappa B2, a member of the NF-kappa B 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-kappa B2(-/-) mice. Moreover, NF-kappa B2(-/-) 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-kappa B2 in the development of medullary thymic epithelial cells and, thus, the control of self-tolerance induction.

• 出版日期2006-12-15