A Role for Lymphotoxin in Primary Sjogren's Disease

作者：Shen, Long; Suresh, Lakshmanan; Wu, Jing; Xuan, Jingxiu; Li, Hong; Zhang, Chongjie; Pankewycz, Oleh; Ambrus, Julian L., Jr.^*

来源：The Journal of Immunology, 2010, 185(10): 6355-6363.

DOI：10.4049/jimmunol.1001520

• AUTOCRINE GROWTH-FACTOR
• SECONDARY LYMPHOID-TISSUES
• NONOBESE DIABETIC MICE
• ALPHA-DEFICIENT MICE
• NECROSIS-FACTOR TNF
• T-CELL RESPONSES
• AUTOIMMUNE-DISEASE
• B-CELLS
• BETA-RECEPTOR
• NOD MICE

The etiology of salivary gland injury in primary Sjogren's disease is not well understood. We have previously described a mouse model of Sjogren's disease, IL-14 alpha transgenic (IL14 alpha TG) mice, which reproduces many of the features of the human disease. We now demonstrate a critical role for lymphotoxin a (LTA) in the pathogenesis of Sjogren's disease in IL14 alpha TG mice. IL14 alpha TG mice express LTA mRNA in their salivary glands and spleen and produce soluble LTA protein in their salivary secretions. When IL14 alpha TG mice were crossed with LTA(-/-) mice, the IL14 alpha TG. LTA(-/-) mice retained normal salivary gland secretions and did not develop either lymphocytic infiltration of their salivary glands or secondary lymphomas. However, both IL14 alpha TG and IL14 alpha TG. LTA(-/-) mice produced similar amounts of IFN-alpha and had similar deposition of autoantibodies in their salivary glands. Both IL14 alpha and IL14 alpha/LTA(-/-) mice had similar B cell responses to T-dependent and T-independent Ags, L-selectin expression, and expression of RelA, RelB, and NF-kappa B2 in their spleens. These studies suggest that LTA plays a critical role in the local rather than systemic inflammatory process of Sjogren's disease. Furthermore, local production of soluble LTA in the salivary glands of IL14 alpha TG mice is necessary for the development of overt Sjogren's disease. Autoantibody deposition alone is not sufficient to produce salivary gland dysfunction. We also demonstrate that LTA is increased in the salivary gland secretions and sera of patients with Sjogren's disease, further strengthening the biological relevance of the IL14 alpha TG model to understanding the pathogenesis of human disease. The Journal of Immunology, 2010, 185: 6355-6363.

• 出版日期2010-11-15
• 单位四川大学