The IL‐14alpha Transgenic Mouse as a Model for Sjogren Disease

Abstract

Sjogren's disease is a common autoimmune disease with both local (loss of salivary gland function) and systemic manifestations. Current animal models replicate only particular aspects of the disease. We have developed an animal model for Sjogren's disease by expressing IL‐14alpha, a gene expressed at high levels in both human Sjogren's disease and various animal models of Sjogren's syndrome, as a transgene in C57BL/6 mice. The IL‐14alpha transgenic mice (IL‐14a TG) accurately simulate human Sjogren's disease with hypergammaglobulinemia, autoantibodies, infiltration of the submandibular glands followed by the parotid glands with lymphocytes, interstitial lung disease, mild kidney disease and in old age large B cell lymphomas. We further demonstrate the loss of salivary gland function occurs before infiltration of the salivary glands with lymphocytes, but after deposition of immunoglobulins is noted in the salivary glands. We demonstrate that lymphotoxin is present in the salivary gland secretions before salivary gland function is lost. IL‐14aTG mice deficient in lymphotoxin fail to develop loss of salivary gland function or lymphocytic infiltration of their salivary glands. Thus, the IL‐14a TG mice are a valuable new model to study all aspects of Sjogren's disease. Early injury to the salivary glands likely involves cytokines, including lymphotoxin, and various autoantibodies. This work is supported by the Kaleida Health Foundation.