ID 111495
Author
Han, Hongwei The University of Tokushima
Keywords
autoimmune disease
AIRE
thymic epithelial cell
thymus graft
bone-marrow transfer
Content Type
Journal Article
Description
Physical contact between thymocytes and the thymic stroma is essential for the establishment of self-tolerance, and Aire in thymic epithelial cells plays an important role in this action. As expected, the autoimmune phenotypes of Aire-deficient mice are thymic stroma-dependent. Interestingly, the spectrum of the organs involved differs depending on the genetic background of non-autoimmune-prone mouse strains. Furthermore, deficiency of Aire in an autoimmune-prone strain of NOD also modifies target-cell specificity in the pancreas. In order to clarify the factors that regulate target-organ specificity in Aire-dependent autoimmunity, I have generated both thymic and bone-marrow chimeras, making it possible to evaluate the contribution of thymic stroma and bone-marrow-derived cells to this pathogenic process. The findings suggested that the genetic background of bone-marrow-derived cells contributes to the strain-dependent target-organ specificity of non-autoimmune-prone strains. Furthermore, in a study using NOD mice with a fixed genetic background, thymic stromal cells but not bone-marrow- derived cells were found to be relevant to the Aire-dependent alteration of target-cell specificity in the pancreas. These results clearly underscore the significance of immunological and/or genetic complexity that underlies Aire-deficiency monogenic disease together with critical dialogue between thymic stroma and bone-marrow-derived cells in the organized thymic microenvironment.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
54
Issue
1-2
Start Page
54
End Page
64
Sort Key
54
Published Date
2007-02
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher