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 C Levitt, Jean Christophe Renauld

Research output: Contribution to journalArticle

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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
Pages (from-to)3244-3251
Number of pages8
JournalJournal of Immunology
Volume178
Issue number5
StatePublished - Mar 1 2007
Externally publishedYes

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Interleukin-9
Interleukin-13
Epithelial Cells
Lung
Interleukin-9 Receptors
Mucus
Mastocytosis
Eosinophilia
Eosinophils
B-Lymphocytes
Asthma
Phenotype
Interleukin-5
Peritoneal Cavity
Mast Cells
Interleukin-4
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Steenwinckel, V., Louahed, J., Orabona, C., Huaux, F., Warnier, G., McKenzie, A., ... 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.

IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells. / Steenwinckel, Valérie; Louahed, Jamila; Orabona, Ciriana; Huaux, François; Warnier, Guy; McKenzie, Andrew; Lison, Dominique; Levitt, Roy C; Renauld, Jean Christophe.

In: Journal of Immunology, Vol. 178, No. 5, 01.03.2007, p. 3244-3251.

Research output: Contribution to journalArticle

Steenwinckel, V, Louahed, J, Orabona, C, Huaux, F, Warnier, G, McKenzie, A, Lison, D, Levitt, RC & Renauld, JC 2007, 'IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells', Journal of Immunology, vol. 178, no. 5, pp. 3244-3251.
Steenwinckel V, Louahed J, Orabona C, Huaux F, Warnier G, McKenzie A et al. IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells. Journal of Immunology. 2007 Mar 1;178(5):3244-3251.
Steenwinckel, Valérie ; Louahed, Jamila ; Orabona, Ciriana ; Huaux, François ; Warnier, Guy ; McKenzie, Andrew ; Lison, Dominique ; Levitt, Roy C ; Renauld, Jean Christophe. / IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells. In: Journal of Immunology. 2007 ; Vol. 178, No. 5. pp. 3244-3251.
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AU - Louahed, Jamila

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AU - Warnier, Guy

AU - McKenzie, Andrew

AU - Lison, Dominique

AU - Levitt, Roy C

AU - Renauld, Jean Christophe

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