Development of autoimmunity in IL-14alpha-transgenic mice.
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| Abstract |
Multiple genetic loci contribute to the development of systemic lupus erythematosus (SLE). In murine models for SLE, various genes on chromosome four have been implicated. IL-14 is a cytokine originally identified as a B cell growth factor. The il14 gene is located on chromosome 4. IL-14alpha is a cytokine encoded by the plus strand of the IL-14 gene using exons 3-10. The expression of IL-14alpha is increased in (NZB x NZW)F1 mice. In this study, we produced IL-14alpha-transgenic mice to study the role of IL-14alpha in the development of autoimmunity. At age 3-9 mo, IL-14alpha-transgenic mice demonstrate increased numbers of B1 cells in the peritoneum, increased serum IgM, IgG, and IgG 2a and show enhanced responses to T-dependent and T-independent Ags compared with littermate controls. At age 9-17 mo, IL-14alpha-transgenic mice develop autoantibodies, sialadenitis, as in Sjögren's syndrome, and immune complex-mediated nephritis, as in World Health Organization class II SLE nephritis. Between the ages 14-18 mo, 95% of IL-14alpha-transgenic mice developed CD5+ B cell lymphomas, consistent with the lymphomas seen in elderly patients with Sjögren's syndrome and SLE. These data support a role for IL-14alpha in the development of both autoimmunity and lymphomagenesis. These studies may provide a genetic link between these often related disorders.
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| Authors | Long Shen, Chongjie Zhang, Tao Wang, Stephen Brooks, Richard J Ford, Yen Chiu Lin-Lee, Amy Kasianowicz, Vijay Kumar, Lisa Martin, Ping Liang, John Cowell, Julian L Ambrus Jr |
| Journal | Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 177 Issue 8 Pg. 5676-86 (Oct 15 2006) ISSN: 0022-1767 [Print] United States |
| PMID | 17015757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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