Autoimmunity-aging mouse model for autoimmune diseases

Abstract

Recent evidences suggest that the apoptotic pathway plays a central role in tolerazing T-cells to tissue-specific self-antigen, and may drive the age-related autoimmune phenomenon. Primary Sjögren's syndrome (SS) is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the exocrine glands, and systemic production of autoantibodies to the ribonucleoprotein (RNP) particles SS-A/Ro and SS-B/La. It can be considered that a defect in activation induced cell death (AICD) of effector T-cells may result in the progression of autoimmune exocrinopathy in SS. We found that aging-associated disturbances in T-cell homeostasis are accelerated in the animal model with SS, resulting in the development of extraglandular manifestation including autoimmune arthritis and interstitial pneumonia. We demonstrated that tissue-specific apoptosis may contribute to autoantigen cleavage, leading to the age-related acceleration of autoimmune exocrinopathy. The immune system undergoes profound changes with advancing age that are beginning to be understood and that need to be incorporated into the pathogenesis of SS. The studies reviewed the molecular mechanisms on aging-associated progression in animal model of autoimmune exocrinopathy.