Spontaneous autoimmunity prevented by thymic expression of a single self-antigen.
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.
DeVoss
Jason
J
Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Hou
Yafei
Y
Johannes
Kellsey
K
Lu
Wen
W
Liou
Gregory I
GI
Rinn
John
J
Chang
Howard
H
Caspi
Rachel R
RR
Caspi
Rachel
R
Fong
Lawrence
L
Anderson
Mark S
MS
D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control*; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D012177:Retinol-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D014605:Uveitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000096927:AIRE Protein; D000099214:Retinol-Binding Proteins, Interstitial
D001324:Autoantigens; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; D000099214:Retinol-Binding Proteins, Interstitial