Lymphomagenesis, hydronephrosis, and autoantibodies result from dysregulation of IL-9 and are differentially dependent on Th2 cytokines.

A. J. Lauder, H. E. Jolin, P. Smith, J. G. van den Berg, A. Jones, William Wisden, K. G. Smith, A. Dasvarma, P. G. Fallon, A. N. J. McKenzie

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    11 Citations (Scopus)

    Abstract

    Interleukin-9 is an immunoregulatory cytokine implicated in the development of asthma and allergy. To investigate the role of IL-9 in vivo, we have generated transgenic mice in which IL-9 is expressed from its own promoter. Strikingly, overexpression of IL-9 resulted in premature mortality associated with a complex phenotype characterized by the development of autoantibodies, hydronephrosis, and T cell lymphoma. By intercrossing IL-9 transgenic mice with a panel of Th2 cytokine-deficient mice, we demonstrate that these disorders represent distinct phenotypes that can be dissociated by their differential dependence on Th2 cytokines. Autoantibody production was ablated in IL-9 transgenic animals with a combined absence of IL-4, IL-5, and IL-13, coincident with a reduction in peritoneal B-1 cells. Hydronephrosis arose in 75% of IL-9 transgenic animals and was dependent on the presence of IL-4 and IL-13. In contrast, T cell lymphomas developed independently of the other Th2 cytokines, with the generation of rapidly proliferating CD8(+) or CD4(+)CD8(+) T cell clones that arose in the thymus before infiltrating both lymphoid and nonlymphoid tissues. Our data highlight potentially important new roles for IL-9, through its regulation of downstream Th2 effector cytokines, in autoantibody production and in hydronephrosis.

    Original languageEnglish
    Pages (from-to)113-122
    Number of pages9
    JournalThe Journal of Immunology
    Volume173
    Publication statusPublished - 2004

    Keywords

    • CELL GROWTH FACTOR-P40
    • TRANSGENIC MICE
    • B-1 CELLS
    • EOSINOPHILIC CYSTITIS
    • SCHISTOSOME INFECTION
    • AUTOIMMUNE SYMPTOMS
    • INTERLEUKIN (IL)-4
    • HEPATIC-FIBROSIS
    • EXPRESSION
    • MOUSE

    Cite this

    Lauder, A. J., Jolin, H. E., Smith, P., van den Berg, J. G., Jones, A., Wisden, W., ... McKenzie, A. N. J. (2004). Lymphomagenesis, hydronephrosis, and autoantibodies result from dysregulation of IL-9 and are differentially dependent on Th2 cytokines. The Journal of Immunology, 173, 113-122.