| First Author | Lauder AJ | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 1 | Pages | 113-22 |
| PubMed ID | 15210765 | Mgi Jnum | J:90927 |
| Mgi Id | MGI:3045527 | Citation | Lauder AJ, et al. (2004) Lymphomagenesis, hydronephrosis, and autoantibodies result from dysregulation of IL-9 and are differentially dependent on Th2 cytokines. J Immunol 173(1):113-22 |
| abstractText | 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. |
