Development of autoimmunity in IL-14α-transgenic mice

Long Shen, Chongjie Zhang, Tao Wang, Stephen Brooks, Richard J. Ford, Yen Chui Lin-Lee, Amy Kasianowicz, Vijay Kumar, Lisa Martin, Ping Liang, John Kenneth Cowell, Julian L. Ambrus

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60 Scopus citations

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-14α is a cytokine encoded by the plus strand of the IL-14 gene using exons 3-10. The expression of IL-14α is increased in (NZB × NZW)F1 mice. In this study, we produced IL-14α-transgenic mice to study the role of IL-14α in the development of autoimmunity. At age 3-9 mo, IL-14α-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-14α-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-14α-transgenic mice developed CD5+ B cell lymphomas, consistent with the lymphornas seen in elderly patients with Sjögren's syndrome and SLE. These data support a role for IL-14α in the development of both autoimmunity and lymphomagenesis. These studies may provide a genetic link between these often related disorders.

Original languageEnglish (US)
Pages (from-to)5676-5686
Number of pages11
JournalJournal of Immunology
Volume177
Issue number8
DOIs
StatePublished - Oct 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Shen, L., Zhang, C., Wang, T., Brooks, S., Ford, R. J., Lin-Lee, Y. C., Kasianowicz, A., Kumar, V., Martin, L., Liang, P., Cowell, J. K., & Ambrus, J. L. (2006). Development of autoimmunity in IL-14α-transgenic mice. Journal of Immunology, 177(8), 5676-5686. https://doi.org/10.4049/jimmunol.177.8.5676