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T cell development is tightly controlled by thymic stromal cells. Alterations in stromal architecture affect T cell maturation and the development of self-tolerance. The monogenic autoimmune syndrome APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy) is characterized by the loss of self-tolerance to multiple organs. Although mutations in the autoimmune regulator (AIRE) gene are responsible for this disease, the function of AIRE is not known. Here we report on the spatial and temporal pattern of murine Aire expression during thymic ontogeny and T cell selection. Early during development, thymic Aire transcription is critically dependent on RelB and occurs in epithelial cells in response to lymphocyte-mediated signals. In adult tissue, Aire expression is confined to the medulla and the corticomedullary junction, where it is modulated by thymocytes undergoing negative selection. Aire may determine thymic stromal organization and with it the induction of self-tolerance.

Original publication

DOI

10.4049/jimmunol.165.4.1976

Type

Journal article

Journal

J Immunol

Publication Date

15/08/2000

Volume

165

Pages

1976 - 1983

Keywords

Animals, Cell Communication, Cell Differentiation, Embryonic and Fetal Development, Epithelial Cells, Gene Expression Regulation, Immune Tolerance, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Polyendocrinopathies, Autoimmune, Proto-Oncogene Proteins, RNA, Messenger, Stromal Cells, Thymus Gland, Transcription Factor RelB, Transcription Factors, Transcription, Genetic