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

Research output: Contribution to journalArticle

57 Citations (Scopus)

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
StatePublished - Oct 15 2006
Externally publishedYes

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Autoimmunity
Systemic Lupus Erythematosus
Transgenic Mice
Immunoglobulin G
Interleukin-9
Sialadenitis
Cytokines
Genes
Chromosomes, Human, Pair 4
Lupus Nephritis
Genetic Loci
Interleukin-17
Nephritis
Peritoneum
B-Cell Lymphoma
Antigen-Antibody Complex
Autoantibodies
Immunoglobulin M
Exons
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Shen, L., Zhang, C., Wang, T., Brooks, S., Ford, R. J., Lin-Lee, Y. C., ... Ambrus, J. L. (2006). Development of autoimmunity in IL-14α-transgenic mice. Journal of Immunology, 177(8), 5676-5686.

Development of autoimmunity in IL-14α-transgenic mice. / Shen, Long; Zhang, Chongjie; Wang, Tao; Brooks, Stephen; Ford, Richard J.; Lin-Lee, Yen Chui; Kasianowicz, Amy; Kumar, Vijay; Martin, Lisa; Liang, Ping; Cowell, John Kenneth; Ambrus, Julian L.

In: Journal of Immunology, Vol. 177, No. 8, 15.10.2006, p. 5676-5686.

Research output: Contribution to journalArticle

Shen, L, Zhang, C, Wang, T, Brooks, S, Ford, RJ, Lin-Lee, YC, Kasianowicz, A, Kumar, V, Martin, L, Liang, P, Cowell, JK & Ambrus, JL 2006, 'Development of autoimmunity in IL-14α-transgenic mice', Journal of Immunology, vol. 177, no. 8, pp. 5676-5686.
Shen L, Zhang C, Wang T, Brooks S, Ford RJ, Lin-Lee YC et al. Development of autoimmunity in IL-14α-transgenic mice. Journal of Immunology. 2006 Oct 15;177(8):5676-5686.
Shen, Long ; Zhang, Chongjie ; Wang, Tao ; Brooks, Stephen ; Ford, Richard J. ; Lin-Lee, Yen Chui ; Kasianowicz, Amy ; Kumar, Vijay ; Martin, Lisa ; Liang, Ping ; Cowell, John Kenneth ; Ambrus, Julian L. / Development of autoimmunity in IL-14α-transgenic mice. In: Journal of Immunology. 2006 ; Vol. 177, No. 8. pp. 5676-5686.
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