NF-kappaB2 is required for the control of autoimmunity by regulating the development of medullary thymic epithelial cells.
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.
Zhang
Baochun
B
Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3035 Arlington Avenue, Toledo, OH 43614, USA.
Wang
Zhe
Z
Ding
Jane
J
Peterson
Pärt
P
Gunning
William T
WT
Ding
Han-Fei
HF
D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology*; D004847:Epithelial Cells / Q000166:cytology; D005455:Fluorescent Antibody Technique; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D016328:NF-kappa B