Antagonistic Roles of Thymic Stromal Lymphopoietin (TSLP) and Surfactant Protein-D (SP-D) in Dendritic Cell Regulation During Ozone-Induced Exacerbation of Allergic Airway Inflammation in Mice

Angela Haczku, MD, PhD, FAAAAI, Blerina Kokalari, Moyar Q. Ge, Cynthia Koziol-White, Imre Redai, Martine Loubeau, Carla Bauer, Christopher Stevenson, Lisa R. Forbes, MD

Abstract: 

Rationale

The immunoprotective lung collectin, SP-D and the epithelial-derived cytokine, TSLP target common cells in response to airway injury. We hypothesized that SP-D and TSLP regulate dendritic cell function in response to ozone-induced lung injury in allergen-exposed mice.

Methods

SP-D deficient mice, wild type (wt) C57BL/6 mice, and low SP-D expressor Balb/c mice sensitized and challenged with Aspergillus fumigatus allergenic extract or mock sensitized controls were subsequently exposed to ozone (2 ppm) or air for 2h. Cytokine and SP-D expression was measured by immunoassay and Taqman. Dendritic cell (DC) phenotypes and CCL17 production were studied by FACS analysis. Direct effects of TSLP and SP-D on DC maturation were investigated using bone-marrow derived DCs (BMDCs) and anti-TSLPR.

Results

Acute, transient increases in TSLP expression preceded increased BAL SP-D levels following ozone exposure of C57BL/6 and Balb/c mice. Ozone exposure increased myeloid (CD11b+CD11c+) DC (mDC) activation and airway inflammation in BALB/c, but not C57BL/6 mice, previously sensitized and challenged with allergen. Increases in BAL mDC numbers were associated with increased TSLP mRNA expression in SP-D-/- but not wt mice after combining ozone and allergen exposure. In BMDCs the presence of SP-D or anti-TSLPR suppressed intracellular expression of CCL17 in CD11c cells, which was dose-dependently reversed by exogenously added TSLP.

Conclusions

Low levels of SP-D may predispose to ozone-induced airway inflammation through TSLP-mediated activation and mobilization of CD11b+ mDCs. Negative regulation of pulmonary DC activation by SP-D is important for reducing chronic inflammatory changes in the airways after allergen and ozone exposures.

Journal of Allergy and Clinical Immunology, Vol. 131, Issue 2, AB61

http://dx.doi.org/10.1016/j.jaci.2012.12.1540

abstract No: 

219
    • AAAAI 2013 (69th)