Progress in understanding autoimmune exocrinopathy using the non-obese diabetic mouse: an update.
Sjögren's Syndrome (SS) is a chronic autoimmune disease characterized by histological and functional alterations of salivary and lacrimal glands that result in a severe dryness of the mouth and the eyes. The etiology of SS has remained undefined despite investigators' significant efforts to identify the mechanisms of initiation. Based on histopathology, several animal models are available--such as MRL/lpr, NZW/NZB, NFS/sld, graft vs. host, transgenic mouse expressing viral surface antigen, and the non-obese diabetic (NOD) mouse--for investigation of the etiology of SS. Biochemical and immunological similarities between human SS and autoimmune exocrinopathy (AEC) in the NOD mouse, including the loss of secretory function, establish the NOD mouse as an appropriate model to unravel the underlying pathophysiology of SS. Recently, several NOD congenic partner strains have been developed to investigate the roles of genetic intervals, cytokines, and autoantibodies in the disease pathogenesis. Studies on NOD-scid suggest that the pathogenesis of SS occurs in two phases: an asymptomatic phase, in which epithelial cells of exocrine tissues undergo dedifferentiation accompanied by elevated apoptosis; and a second phase in which autoaggression is mounted against target organ autoantigens, resulting in the activation of T- and B-cells, and the generation of autoantibodies. The presence of autoantibodies on the cell-surface signaling receptor, the muscarinic(3) receptor, in both SS patients and the NOD mice correlates with the hallmark clinical symptom of secretory dysfunction. Additionally, the NOD mouse model provides an important example of how both Th1 and Th2 cytokines, as well as non-immune genetic loci, are involved in the maintenance of and progression to the overt disease state. Ultimately, analysis of these data provides insight into potentially novel therapeutic interventions.
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Department of Oral Biology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA. scha@dental.ufl.edu
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D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D005088:Exocrine Glands / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D043587:Receptor, Muscarinic M3 / Q000276:immunology; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology*
D043587:Receptor, Muscarinic M3