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Toll-like receptor 6 drives interleukin-17A expression during experimental hypersensitivity pneumonitis.

Authors: Fong, DJ  Hogaboam, CM  Matsuno, Y  Akira, S  Uematsu, S  Joshi, AD 
Citation: Fong DJ, etal., Immunology. 2010 May;130(1):125-36. Epub 2010 Jan 11.
Pubmed: (View Article at PubMed) PMID:20070409
DOI: Full-text: DOI:10.1111/j.1365-2567.2009.03219.x

Hypersensitivity pneumonitis (HP) is a T-cell-driven disease that is histologically characterized by diffuse mononuclear cell infiltrates and loosely formed granulomas in the lungs. We have previously reported that interleukin-17A (IL-17A) contributes to the development of experimental HP, and that the pattern recognition receptor Toll-like receptor 6 (TLR6) might be a factor in the initiation of this response. Using a well-established murine model of Saccharopolyspora rectivirgula-induced HP, we investigated the role of TLR6 in the immunopathogenesis of this disease. In the absence of TLR6 signalling, mice that received multiple challenges with S. rectivirgula-antigen (SR-Ag) had significantly less lung inflammation compared with C57BL/6 mice (wild-type; WT) similarly challenged with SR-Ag. Flow cytometric analysis of whole lung samples from SR-Ag-challenged mice showed that TLR6(-/-) mice had a decreased CD4(+) : CD8(+) T-cell ratio compared with WT mice. Cytokine analysis at various days after the final SR-Ag challenge revealed that whole lungs from TLR6(-/-) mice contained significantly less IL-17A than lungs from WT mice with HP. The IL-17A-driving cytokines IL-21 and IL-23 were also expressed at lower levels in SR-Ag-challenged TLR6(-/-) mice, when compared with SR-Ag-challenged WT mice. Other pro-inflammatory cytokines, namely interferon-gamma and RANTES, were also found to be regulated by TLR6 signalling. Anti-TLR6 neutralizing antibody treatment of dispersed lung cells significantly impaired SR-Ag-induced IL-17A and IL-6 generation. Together, these results indicate that TLR6 plays a pivotal role in the development and severity of HP via its role in IL-17A production.

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CRRD Object Information
CRRD ID: 4889532
Created: 2010-12-03
Species: All species
Last Modified: 2010-12-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.