TY - JOUR
T1 - NF-κB2 is required for the control of autoimmunity by regulating the development of medullary thymic epithelial cells
AU - Zhang, Baochun
AU - Wang, Zhe
AU - Ding, Jane
AU - Peterson, Pärt
AU - Gunning, William T.
AU - Ding, Han Fei
PY - 2006/12/15
Y1 - 2006/12/15
N2 - 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-κB2, a member of the NF-κB 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-κB2-/- mice. Moreover, NF-κB2-/- 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-κB2 in the development of medullary thymic epithelial cells and, thus, the control of self-tolerance induction.
AB - 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-κB2, a member of the NF-κB 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-κB2-/- mice. Moreover, NF-κB2-/- 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-κB2 in the development of medullary thymic epithelial cells and, thus, the control of self-tolerance induction.
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U2 - 10.1074/jbc.M606705200
DO - 10.1074/jbc.M606705200
M3 - Article
C2 - 17046818
AN - SCOPUS:33845996957
SN - 0021-9258
VL - 281
SP - 38617
EP - 38624
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 50
ER -