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

Angela Franciska 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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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 (US)
Pages (from-to)3557-3565
Number of pages9
JournalJournal of Immunology
Volume176
Issue number6
StatePublished - Mar 15 2006

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Pulmonary Surfactant-Associated Protein D
Interleukin-13
Interleukin-4
Aspergillus fumigatus
Allergens
Lung
Chemokine CCL17
Alveolar Epithelial Cells
Th2 Cells
Messenger RNA
Proteins
Knockout Mice
Immunoglobulin E
Inhalation
Cell Count
Immunoglobulin G
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Haczku, A. F., Cao, Y., Vass, G., Kierstein, S., Nath, P., Atochina-Vasserman, E. N., ... 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.

IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. / Haczku, Angela Franciska; Cao, Yang; Vass, Geza; Kierstein, Sonja; Nath, Puneeta; Atochina-Vasserman, Elena N.; Scanlon, Seth T.; Li, Lily; Griswold, Don E.; Chung, K. Fan; Poulain, Francis R; Hawgood, Samuel; Beers, Michael F.; Crouch, Erika C.

In: Journal of Immunology, Vol. 176, No. 6, 15.03.2006, p. 3557-3565.

Research output: Contribution to journalArticle

Haczku, AF, Cao, Y, Vass, G, Kierstein, S, Nath, P, Atochina-Vasserman, EN, Scanlon, ST, Li, L, Griswold, DE, Chung, KF, Poulain, FR, Hawgood, S, Beers, MF & Crouch, EC 2006, 'IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response', Journal of Immunology, vol. 176, no. 6, pp. 3557-3565.
Haczku AF, Cao Y, Vass G, Kierstein S, Nath P, Atochina-Vasserman EN et al. IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. Journal of Immunology. 2006 Mar 15;176(6):3557-3565.
Haczku, Angela Franciska ; Cao, Yang ; Vass, Geza ; Kierstein, Sonja ; Nath, Puneeta ; Atochina-Vasserman, Elena N. ; Scanlon, Seth T. ; Li, Lily ; Griswold, Don E. ; Chung, K. Fan ; Poulain, Francis R ; Hawgood, Samuel ; Beers, Michael F. ; Crouch, Erika C. / IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. In: Journal of Immunology. 2006 ; Vol. 176, No. 6. pp. 3557-3565.
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