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

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 eosinophilia, 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 overexpressed 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.

• Authors: Valérie Steenwinckel, Jamila Louahed, Ciriana Orabona, François Huaux, Guy Warnier, Andrew McKenzie, Dominique Lison, Roy Levitt, Jean-Christophe Renauld
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 5 Pg. 3244-51 (Mar 01 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17312173 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl11 protein, mouse
• Chemokine CCL11
• Chemokines, CC
• Il9r protein, mouse
• Interleukin-13
• Interleukin-9
• Receptors, Interleukin-9

Topics

• Animals
• Asthma (genetics, immunology, metabolism, pathology)
• Chemokine CCL11
• Chemokines, CC (biosynthesis, immunology)
• Epithelial Cells (immunology, metabolism, pathology)
• Hematopoietic Stem Cell Transplantation
• Hematopoietic Stem Cells (immunology, metabolism, pathology)
• Interleukin-13 (deficiency, immunology)
• Interleukin-9 (deficiency, immunology)
• Leukocytes (immunology, metabolism, pathology)
• Lung (immunology, metabolism, pathology)
• Mice
• Mice, Knockout
• Mucus (immunology, metabolism)
• Pulmonary Eosinophilia (genetics, immunology, metabolism, pathology)
• Receptors, Interleukin-9 (deficiency, immunology)
• Up-Regulation (immunology)