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 language | English |
|---|---|
| Pages (from-to) | 3557-3565 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 176 |
| Issue number | 6 |
| Publication status | Published - 15 Mar 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. / Haczku, Angela; 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 journal › Article
}
TY - JOUR
T1 - IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response
AU - Haczku, Angela
AU - Cao, Yang
AU - Vass, Geza
AU - Kierstein, Sonja
AU - Nath, Puneeta
AU - Atochina-Vasserman, Elena N.
AU - Scanlon, Seth T.
AU - Li, Lily
AU - Griswold, Don E.
AU - Chung, K. Fan
AU - Poulain, Francis R.
AU - Hawgood, Samuel
AU - Beers, Michael F.
AU - Crouch, Erika C.
PY - 2006/3/15
Y1 - 2006/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33644839256&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644839256&partnerID=8YFLogxK
M3 - Article
C2 - 16517724
AN - SCOPUS:33644839256
VL - 176
SP - 3557
EP - 3565
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -