| First Author | Shen L | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 10 | Pages | 6355-63 |
| PubMed ID | 20952683 | Mgi Jnum | J:165784 |
| Mgi Id | MGI:4838464 | Doi | 10.4049/jimmunol.1001520 |
| Citation | Shen L, et al. (2010) A role for lymphotoxin in primary Sjogren's disease. J Immunol 185(10):6355-63 |
| abstractText | 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-14alpha transgenic (IL14alphaTG) mice, which reproduces many of the features of the human disease. We now demonstrate a critical role for lymphotoxin alpha (LTA) in the pathogenesis of Sjogren's disease in IL14alphaTG mice. IL14alphaTG mice express LTA mRNA in their salivary glands and spleen and produce soluble LTA protein in their salivary secretions. When IL14alphaTG mice were crossed with LTA(-/-) mice, the IL14alphaTG.LTA(-/-) mice retained normal salivary gland secretions and did not develop either lymphocytic infiltration of their salivary glands or secondary lymphomas. However, both IL14alphaTG and IL14alphaTG.LTA(-/-) mice produced similar amounts of IFN-alpha and had similar deposition of autoantibodies in their salivary glands. Both IL14alpha and IL14alpha/LTA(-/-) mice had similar B cell responses to T-dependent and T-independent Ags, L-selectin expression, and expression of RelA, RelB, and NF-kappaB2 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 IL14alphaTG 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 IL14alphaTG model to understanding the pathogenesis of human disease. |
