IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells

Valérie Steenwinckel, Jamila Louahed, Ciriana Orabona, François Huaux, Guy Warnier, Andrew McKenzie, Dominique Lison, Roy Levitt, Jean Christophe Renauld

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Abstract

Increased IL-9 expression, either systemically or under the control of lung-specific promoter, induces an asthma-like phenotype, including mucus overproduction, mastocytosis, lung eosinophiiia, and airway hyperresponsiveness. These activities correlate with increased production of other Th2 cytokines such as IL-4, IL-5, and IL-13 in IL-9 Tg mice. To determine the exact role of IL-13 in this phenotype, mice overexpressing IL-9 were crossed with IL-13-deficient mice. In these animals, IL-9 could still induce mastocytosis and B lymphocyte infiltration of the lungs. Although IL-9-induced eosinophilia in the peritoneal cavity was not diminished in the absence of IL-13, IL-13 was required for IL-9 to increase eotaxin expression and lung eosinophilia. Mucus production and up-regulation of lung epithelial genes upon IL-9 overexpression were completely abolished in the absence of IL-13. Using hemopoietic cell transfer experiments with recipients that overespressed IL-9 but were deficient in the IL-9 receptor (IL-9R), we could demonstrate that the effect of IL-9 on lung epithelial cells is indirect and could be fully restored by transfer of hemopoietic cells expressing IL-9R. Mucus production by lung epithelial cells was only up-regulated when hemopoietic cells simultaneously expressed functional IL-9R and IL-13 genes, indicating that IL-13 is not a cofactor but a direct mediator of the effect of IL-9 on lung epithelial cells. Taken together, these data indicate that IL-9 can promote asthma through IL-13-independent pathways via expansion of mast cells, eosinophils, and B cells, and through induction of IL-13 production by hemopoietic cells for mucus production and recruitment of eosinophils by lung epithelial cells.

Original languageEnglish (US)
Pages (from-to)3244-3251
Number of pages8
JournalJournal of Immunology
Volume178
Issue number5
DOIs
StatePublished - Mar 1 2007

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Steenwinckel, V., Louahed, J., Orabona, C., Huaux, F., Warnier, G., McKenzie, A., Lison, D., Levitt, R., & Renauld, J. C. (2007). IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells. Journal of Immunology, 178(5), 3244-3251. https://doi.org/10.4049/jimmunol.178.5.3244