Document Detail

The Absence of Toll-IL-1 Receptor 8/SIGIRR Reduces House Dust Mite-Induced Allergic Airways Inflammation in Mice.
MedLine Citation:
PMID:  23614768     Owner:  NLM     Status:  Publisher    
Allergic asthma is a chronic inflammatory disease predominately associated with the activation of CD4+ T helper type 2 (Th2) cells. Additionally, it is widely acknowledged that innate pattern recognition receptors shape the adaptive immune response. For example, the activation of airway epithelial TLR4 is necessary for the generation of house dust mite-specific Th2 responses and the development of asthma in mice. Here we sought to determine whether the absence of TIR8, 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 airways hyperreactivity were also significantly reduced in the 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 sensitisation 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 sensitisation 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.
Jessica Barry; Zhixuan Loh; Adam Collison; Stuart Mazzone; Amit Lalwani; Vivian Zhang; Sophia Davidson; Elisha Wybacz; Cecilia Garlanda; Alberto Mantovani; Joerg Mattes; Paul S Foster; Simon Phipps
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-24
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  -     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Centre for Asthma and Respiratory Diseases and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
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