Normal Thymic Architecture and Negative Selection Are Associated with Aire Expression, the Gene Defective in the Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)

• Published in: The Journal of immunology (1950) Vol. 165; no. 4; pp. 1976 - 1983
• Main Authors: Zuklys, Saulius, Balciunaite, Gina, Agarwal, Anni, Fasler-Kan, Elizaveta, Palmer, Ed, Hollander, Georg A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.08.2000
• Subjects: AIRE gene; AIRE Protein; Animals; Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; Cell Communication - genetics; Cell Communication - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Embryonic and Fetal Development - genetics; Embryonic and Fetal Development - immunology; Epithelial Cells - cytology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Gene Expression Regulation - immunology; Immune Tolerance - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Polyendocrinopathies, Autoimmune - genetics; Polyendocrinopathies, Autoimmune - immunology; Polyendocrinopathies, Autoimmune - pathology; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - physiology; RNA, Messenger - biosynthesis; Stromal Cells - cytology; Stromal Cells - immunology; Stromal Cells - metabolism; Thymus Gland - anatomy & histology; Thymus Gland - cytology; Thymus Gland - growth & development; Thymus Gland - immunology; Transcription Factor RelB; Transcription Factors - biosynthesis; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology; Transcription, Genetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.4.1976

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.