We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Lymphotoxin pathway directs thymic Aire expression.
- Authors
Chin, Robert K.; Lo, James C.; Kim, Oliver; Blink, Sarah E.; Christiansen, Peter A.; Peterson, Pärt; Yang Wang; Ware, Carl; Yang-Xin Fu
- Abstract
The autoimmune regulator Aire is a key mediator of central tolerance for peripherally restricted antigens. Its absence in human patients results in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. The cellular signals that regulate Aire expression are undefined. We show here that lymphotoxin signaling is necessary for the expression of Aire and its downstream target genes. The failure of Aire induction in the thymi of lymphotoxin-deficient and lymphotoxin-ß receptor-deficient mice contributes to overt autoimmunity against self antigens normally protected by Aire. Conversely, stimulation of lymphotoxin-ß receptor by agonistic antibody leads to increased expression of Aire and tissue-restricted antigens in both intact thymi and cultured thymic epithelial cell line. These findings define the essential cross-talk between thymocytes and thymic stroma that is required for central tolerance.
- Subjects
TUMOR necrosis factors; GENE expression
- Publication
Nature Immunology, 2003, Vol 4, Issue 11, p1121
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni982