Hayashi, Yoshio The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Ishimaru, Naozumi The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Recent evidences suggest that the apoptotic pathway plays a central role in tolerazing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon in the salivary glands. We found that retinoblastoma-associated protein RbAp48 overexpression induces p53-mediated apoptosis in the salivary glands caused by estrogen deficiency. We demonstrated that transgenic (Tg) expression of RbAp48 resulted in the development of autoimmune exocrinopathy resembling Sjögren’s syndrome (SS). CD4+T cell-mediated autoimmune lesions in the salivary glands were aggravated with age, in association with autoantibody productions. We obtained evidences that salivary epithelial cells can produce interferon-γ(IFN-γ) besides interleukin (IL)-18, which activates interferon regulatory factor-1 (IRF-1), and class II transactivator (CIITA). Indeed, the autoimmune lesions into Rag2-/- mice were induced by the adoptive transfer of lymph node cells from RbAp48-Tg mice. These results indicate a novel immunocompetent role of epithelial cells that can produce IFN-γ, resulting in loss of local tolerance prior to developing gender-based autoimmunity. The studies reviewed the molecular mechanisms on the development of salivary gland autoimmunity, and gender-related differences in SS.
The Journal of Medical Investigation
Faculty of Medicine Tokushima University
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jmi_56_suppl_185.pdf 462 KB