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IL-17A-expressing T cells are essential for bacterial clearance in a murine model of hypersensitivity pneumonitis.

Authors: Simonian, PL  Roark, CL  Wehrmann, F  Lanham, AM  Born, WK  O'Brien, RL  Fontenot, AP 
Citation: Simonian PL, etal., J Immunol. 2009 May 15;182(10):6540-9.
Pubmed: (View Article at PubMed) PMID:19414809
DOI: Full-text: DOI:10.4049/jimmunol.0900013

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by a diffuse mononuclear cell infiltrate in the lung that can progress to pulmonary fibrosis with chronic exposure to an inhaled Ag. We previously reported that C57BL/6 mice repeatedly exposed to the ubiquitous microorganism Bacillus subtilis develop mononuclear infiltrates in the lung that contain Vgamma6/Vdelta1(+) gammadelta T cells. In the absence of this T cell subset, mice treated with B. subtilis had significantly increased collagen deposition in the lung, suggesting a regulatory role for Vgamma6/Vdelta1(+) gammadelta T cells. To further investigate the role of Vgamma6/Vdelta1(+) gammadelta T cells in B. subtilis-induced lung fibrosis, we exposed transgenic Vgamma6/Vdelta1 mice to this microorganism and found decreased collagen content in the lung compared with wild-type C57BL/6 mice. Cytokine analysis of lung homogenates from wild-type C57BL/6 mice demonstrated increased IL-17A concentrations with repeated exposure to B. subtilis. In the absence of IL-17 receptor signaling, IL-17ra(-/-) mice had delayed clearance of B. subtilis with increased lung inflammation and fibrosis. Although IL-17A was predominantly expressed by Vgamma6/Vdelta1(+) T cells, a compensatory increase in IL-17A expression by CD4(+) T cells was seen in the absence of gammadelta T cells that resulted in similar levels of IL-17A in the lungs of TCRdelta(-/-) and wild-type C57BL/6 mice. In combination, our data suggest an important role for IL-17A-expressing T lymphocytes, both gammadelta and alphabeta T cells, in eliminating this microorganism that prevents excessive inflammation and eventual lung fibrosis in this murine model of B. subtilis-induced hypersensitivity pneumonitis.

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CRRD Object Information
CRRD ID: 5144217
Created: 2011-08-02
Species: All species
Last Modified: 2011-08-02
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.