Spontaneous autoimmunity prevented by thymic expression of a single self-antigen

Jason DeVoss, Yafei Hou, Kellsey Johannes, Wen Lu, Gregory I. Liou, John Rinn, Howard Chang, Rachel Caspi, Lawrence Fong, Mark S. Anderson

Research output: Contribution to journalArticle

202 Scopus citations

Abstract

The expression of self-antigen in the thymus is believed to be responsible for the deletion of autoreactive T lymphocytes, a critical process in the maintenance of unresponsiveness to self. The Autoimmune regulator ( Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome type 1, has been shown to promote the thymic expression of self-antigens. A clear link, however, between specific thymic self-antigens and a single autoimmune phenotype in this model has been lacking. We show that autoimmune eye disease in aire-deficient mice develops as a result of loss of thymic expression of a single eye antigen, interphotoreceptor retinoid-binding protein (IRBP). In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity. These results suggest that failure of thymic expression of selective single self-antigens can be sufficient to cause organ-specific autoimmune disease, even in otherwise self-tolerant individuals. JEM

Original languageEnglish (US)
Pages (from-to)2727-2735
Number of pages9
JournalJournal of Experimental Medicine
Volume203
Issue number12
DOIs
StatePublished - Nov 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    DeVoss, J., Hou, Y., Johannes, K., Lu, W., Liou, G. I., Rinn, J., Chang, H., Caspi, R., Fong, L., & Anderson, M. S. (2006). Spontaneous autoimmunity prevented by thymic expression of a single self-antigen. Journal of Experimental Medicine, 203(12), 2727-2735. https://doi.org/10.1084/jem.20061864