Suppressive effect of IL-4 on IL-13-induced genes in mouse lung

Fred D. Finkelman, Mingyan Yang, Charles Perkins, Kathleen Schleifer, Alyssa Sproles, Jo Anna Santeliz, Jonathan A. Bernstein, Marc E. Rothenberg, Suzanne C. Morris, Marsha Wills-Karp

Research output: Contribution to journalArticlepeer-review

Abstract

Although IL-4 signals through two receptors, IL-4Rα/common γ-chain (γc) and IL-4Rα/IL-13Rα1, 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 α2 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-4Rα/γc suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/γc-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-γ, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)4630-4638
Number of pages9
JournalJournal of Immunology
Volume174
Issue number8
DOIs
StatePublished - Apr 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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