Absence of Toll-IL-1 Receptor 8/Single Immunoglobulin IL-1 Receptor-Related Molecule Reduces House Dust Mite-Induced Allergic Airway Inflammation in Mice

作者：Barry Jessica; Loh Zhixuan; Collison Adam; Mazzone Stuart; Lalwani Amit; Zhang Vivian; Davidson Sophia; Wybacz Elisha; Garlanda Cecilia; Mantovani Alberto; Mattes Joerg; Foster Paul S; Phipps Simon^*

来源：American Journal of Respiratory Cell and Molecular Biology, 2013, 49(3): 481-490.

DOI：10.1165/rcmb.2012-0425OC

• asthma
• TIR8
• house dust mite
• Th2
• IL-1F5

Allergic asthma is a chronic inflammatory disease predominately associated with the activation of CD4(+) T helper Type 2 (Th2) cells. Innate pattern recognition receptors are widely acknowledged to shape the adaptive immune response. For example, the activation of airway epithelial Toll-like receptor-4 (TLR4) is necessary for the generation of house dust mite(HDM)-specific Th2 responses and the development of asthma in mice. Here we sought to determine whether the absence of Toll-interleukin-1 receptor (TIR)-8, a negative regulator of TLR4 signaling that is highly expressed in airway epithelial cells, would exacerbate HDM-induced asthma in a murine model. We found that Th2 but not Th1 or Th17 cytokine expression was significantly reduced in the lung and draining lymph nodes in HDM-sensitized/challenged TIR8 gene-deleted mice. Mucus-producing goblet cells, HDM-specific IgG1, and airway hyperreactivity were also significantly reduced in HDM-exposed, TIR8-deficient mice. Consistent with the attenuated Th2 response, eotaxin-2/CCL24 expression and airway and peribronchial eosinophils were significantly reduced in the absence of TIR8. In contrast, IL-17A-responsive chemokines and neutrophil numbers were unaffected. Similar findings were obtained for cockroach allergen. HDM sensitization alone up-regulated the expression of IL-1F5, a putative TIR8 ligand and inducer of IL-4. Of note, innate IL-4, IL-5, IL-13, and IL-33 cytokine expression was reduced during HDM sensitization in the absence of TIR8, as was the recruitment of conventional dendritic cells and basophils to the draining lymph nodes. Our findings suggest that TIR8 enhances the development of HDM-induced innate and adaptive Th2, but not Th1 or Th17 type immunity.

• 出版日期2013-9