Investigating Early Events in Sjogren’s Disease (135.8)

Abstract

Abstract Little is known about the early events in Sjogren’s disease. Previous studies have demonstrated that interleukin 14 alpha transgenic mice (IL14aTG) replicate the clinical and immunological features of Sjogren’s disease (Clin. Immunol. 130:304, 2009). Salivary gland function is lost before lymphocytic infiltration of the salivary glands. The current studies were designed to investigate the early events involved with salivary gland injury. Western blot studies demonstrated lymphotoxin (LTA) in the salivary gland secretions of IL14aTG mice, while salivary gland function was being lost. IL14aTG mice lacking LTA maintained normal salivary gland structure and function, although autoantibodies were deposited in the salivary glands. Because IL-14aTG mice produce high levels of interferon-a (INF-a) and INF-a can induce production of LTA, we investigated IL14aTG mice lacking the α/β interferon receptor. These mice retained normal salivary gland function, although mild lymphocytic infiltration was noted in the lachrymal glands. Because IL14aTG mice have increased numbers of B1 cells, we produced IL14aTG mice lacking btk. Interestingly, these mice maintained normal salivary gland function despite lymphocytic infiltration of the salivary glands. Thus cytokine injury involving LTA and IFN-a are necessary for the development of salivary gland injury in Sjogren’s disease. The roles of particular autoantibodies and lymphocytic infiltration of the salivary glands need to be elucidated.