Contribution of IL-13 to early exocrinopathy in Id3−/− mice

Id3−/− 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−/− mice. We found that the increase in serum IL-13 levels in Id3−/− mice was largely dependent on αβ T cells. Removal of αβ T cells in Id3−/− 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−/− 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 αβ T cells. Treatment of young Id3−/− 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.

► Id3 disruption results in elevated levels of serum IL-13, increased number of mast cells in salivary glands, and Sjogren's syndrome like disease.
► Mast cell count in gland tissues is inversely correlated to secretory function.
► Id3−/− mice treated with anti-IL-13 show improved saliva production.