IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response

Angela Haczku, Yang Cao, Geza Vass, Sonja Kierstein, Puneeta Nath, Elena N. Atochina-Vasserman, Seth T. Scanlon, Lily Li, Don E. Griswold, K. Fan Chung, Francis R. Poulain, Samuel Hawgood, Michael F. Beers, Erika C. Crouch

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63 Citations (Scopus)

Abstract

The innate immune molecule surfactant protein-D (SP-D) plays an important regulatory role in the allergic airway response. In this study, we demonstrate that mice sensitized and challenged with either Aspergillus fumigatus (Af) or OVA have increased SP-D levels in their lung. SP-D mRNA and protein levels in the lung also increased in response to either rIL-4 or rIL-13 treatment. Type II alveolar epithelial cell expression of IL-4Rs in mice sensitized and challenged with Af, and in vitro induction of SP-D mRNA and protein by IL-4 and IL-13, but not IFN-γ, suggested a direct role of IL-4R-mediated events. The regulatory function of IL-4 and IL-13 was further supported in STAT-6-deficient mice as well as in IL-4/IL-13 double knockout mice that failed to increase SP-D production upon allergen challenge. Interestingly, addition of rSP-D significantly inhibited Af-driven Th2 cell activation in vitro whereas mice lacking SP-D had increased numbers of CD4+ cells with elevated IL-13 and thymus- and activation-regulated chemokine levels in the lung and showed exaggerated production of IgE and IgG1 following allergic sensitization. We propose that allergen exposure induces elevation in SP-D protein levels in an IL-4/IL-13-dependent manner, which in turn, prevents further activation of sensitized T cells. This negative feedback regulatory circuit could be essential in protecting the airways from inflammatory damage after allergen inhalation.

Original languageEnglish
Pages (from-to)3557-3565
Number of pages9
JournalJournal of Immunology
Volume176
Issue number6
Publication statusPublished - 15 Mar 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Haczku, A., Cao, Y., Vass, G., Kierstein, S., Nath, P., Atochina-Vasserman, E. N., Scanlon, S. T., Li, L., Griswold, D. E., Chung, K. F., Poulain, F. R., Hawgood, S., Beers, M. F., & Crouch, E. C. (2006). IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. Journal of Immunology, 176(6), 3557-3565.