Salivary gland and autoimmunity.
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-gamma (IFN-gamma) 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-gamma, 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.
Hayashi
Yoshio
Y
Department of Oral Molecular Pathology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Arakaki
Rieko
R
Ishimaru
Naozumi
N
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D056505:Retinoblastoma-Binding Protein 4 / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology* / Q000473:pathology; D012727:Sex Characteristics; D012859:Sjogren's Syndrome / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D056505:Retinoblastoma-Binding Protein 4