J Immunol. 2010 Apr 15;184(8):4236-46. Epub 2010 Mar 17.
DeVoss JJ, LeClair NP, Hou Y, Grewal NK, Johannes KP, Lu W, Yang T, Meagher C, Fong L, Strauss EC, Anderson MS.
Diabetes Center, University of California-San Francisco, San Francisco, CA 94143, USA.
Sjögren's Syndrome (SS) is a human autoimmune disease characterized by immune-mediated destruction of the lacrimal and salivary glands. In this study, we show that the Aire-deficient mouse represents a new tool to investigate autoimmune dacryoadenitis and keratoconjunctivitis sicca, features of SS. Previous work in the Aire-deficient mouse suggested a role for alpha-fodrin, a ubiquitous Ag, in the disease process. Using an unbiased biochemical approach, however, we have identified a novel lacrimal gland autoantigen, odorant binding protein 1a, targeted by the autoimmune response. This novel autoantigen is expressed in the thymus in an Aire-dependent manner. The results from our study suggest that defects in central tolerance may contribute to SS and provide a new and clinically relevant model to investigate the pathogenic mechanisms in lacrimal gland autoimmunity and associated ocular surface sequelae
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