Contribution of IL-13 to early exocrinopathy in Id3 super(&; minus; /&; minus; mice)

Id3 super(-/- mice represent a model for T cell mediated primary Sjogren's syndrome (PSS). An intriguing feature of this disease model is the early appearance of impaired salivary function or exocrinopathy prior to lymphocytic infiltration of the salivary glands. This phenomenon prompted us to examine the role of cytokines produced by T cells in the systemic regulation of gland function. A comprehensive examination of serum cytokine profiles revealed elevated levels of IL-13 in Id3) super(-)/- mice. We found that the increase in serum IL-13 levels in Id3 super(-/- mice was largely dependent on I+/-I) super(2)T cells. Removal of I+/-I super(2) T cells in Id3 super(-/- mice also eliminates disease symptoms, including lymphocytic infiltration in the gland tissues, and impaired saliva production. We further show that the number of mast cells in the salivary glands of Id3) super(-)/- mice is significantly increased, in a trend inversely related to the saliva production. This increase in the number of mast cells is also dependent on the presence of I+/-I super(2) T cells. Treatment of young Id3 super(-/- mice with anti-IL-13 antibodies over a two-month period resulted in a reduction of both serum IL-13 levels and the number of mast cells in the salivary gland tissues, as well as correspondingly improved saliva production. These findings indicate a potentially important role for IL-13 in gland regulation and disease pathology.)