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  • The role of Aire in clonal selection
  • Taniguchi RT; Anderson MS
  • Immunol Cell Biol 2011[Jan]; 89 (1): 40-4
  • In his clonal selection theory, Frank Macfarlane Burnet predicted that autoreactive lymphocytes are deleted to prevent autoimmunity. This and other principles of lymphocyte behavior outlined by Burnet guided many studies that lead to our current understanding of thymic selection. Thus, when the genetic mutation responsible for autoimmune polyglandular syndrome type 1 was mapped to the autoimmune regulator (AIRE) gene, and Aire was found to be highly expressed in thymic epithelium, studying the role of Aire in negative selection made sense in the context of modern models of thymic selection. We now know Aire is a transcription factor required for the expression of many tissue-specific antigens (TSAs) in the thymus. In the absence of functional Aire, human patients and mice develop multi-organ autoimmune disease because of a defect in thymic negative selection. In addition to its role in the thymus, recent work in our lab suggests that extrathymic Aire-expressing cells have an important role in the clonal deletion of autoreactive CD8+ T cells. In this review, we summarize the latest studies on thymic and peripheral Aire-expressing cells, as well as other TSA-expressing stromal cell populations in peripheral lymphoid organs. We also discuss theoretical differences in thymic and peripheral Aire function that warrant further studies.
  • |Animals[MESH]
  • |Autoimmunity/immunology[MESH]
  • |Clonal Deletion/genetics/*immunology[MESH]
  • |Humans[MESH]
  • |Immune Tolerance/genetics/immunology[MESH]
  • |Polyendocrinopathies, Autoimmune/genetics[MESH]
  • |T-Lymphocytes/immunology/metabolism[MESH]
  • |Thymus Gland/immunology/metabolism[MESH]
  • |Transcription Factors/genetics/*metabolism[MESH]

  • *{{pmid21079643}}
    *<b>[ The role of Aire in clonal selection ]</b> Immunol Cell Biol 2011; 89(1) ; 40-4 Taniguchi RT; Anderson MS


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    Immunol Cell Biol

    40 1.89 2011