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* Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45267;
Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45220; and Divisions of
Immunobiology and
Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229
Although IL-4 signals through two receptors, IL-4R
/common 
-chain (c) and IL-4R/IL-13R1, and only the latter is also activated by IL-13, IL-13 contributes more than IL-4 to goblet cell hyperplasia and airway hyperresponsiveness in murine asthma. To determine whether unique gene induction by IL-13 might contribute to its greater proasthmatic effects, mice were inoculated intratracheally with IL-4 or IL-13, and pulmonary gene induction was compared by gene microarray and real-time PCR. Only the collagen 2 type VI (Ca2T6) gene and three small proline-rich protein (SPRR) genes were reproducibly induced >4-fold more by IL-13 than by IL-4. Preferential IL-13 gene induction was not attributable to B cells, T cells, or differences in cytokine potency. IL-4 signaling through IL-4R/c suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/c-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN- production does not suppress the Ca2T6 or SPRR genes. Thus, IL-4 induces genes in addition to IL-12 that suppress STAT6-mediated SPRR gene induction. These results provide a potential explanation for the dominant role of IL-13 in induction of goblet cell hyperplasia and airway hyperresponsiveness in asthma.
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