A role for lymphotoxin in primary Sjögren's Disease (137.34)

Abstract

Abstract The etiology of salivary gland injury in primary Sjögren's disease is poorly understood. Increased expression of lymphotoxin (LT) has been demonstrated in patients with Sjögren's disease. The current studies were designed to determine whether LT contributes to early salivary gland injury in a murine model of Sjogren's disease, IL-14alpha transgenic mice (IL-14α TG). Lymphotoxin mRNA and protein is found in the salivary glands of IL-14αTG mice as early as 3 months of age. IL-14αTG.LT-/- mice retained normal salivary gland secretions and failed to develop lymphocytic infiltration of their salivary glands. However, deposition of IgM antibodies in the salivary glands and infiltration of the lungs still occurred in IL-14αTG.LTA-/- mice. B cell subpopulations and responses to T-dependent and T-independent antigens were similar in IL-14αTG and IL-14αTG.LTA-/- mice. These studies suggest that locally produced LT may cause direct injury to the salivary glands in IL-14α TG mice. There can be discordance between antibody deposition in the salivary glands and salivary gland dysfunction. The mechanisms of salivary gland and lung injury in Sjogren's disease may differ. Further studies are needed to determine the roles of LT in early injury to the salivary glands in IL-14α TG mice and patients with Sjögren's disease.