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IL-17A-Expressing T Cells Are Essential for Bacterial Clearance in a Murine Model of Hypersensitivity Pneumonitis¹

Philip L. Simonian^2,*, Christina L. Roark, Fabian Wehrmann^*, Allison M. Lanham^*, Willi K. Born, Rebecca L. O'Brien and Andrew P. Fontenot^*,

^* Department of Medicine, University of Colorado Denver, Aurora, CO 80045; and Integrated Department of Immunology, National Jewish Health, Denver, CO 80206

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 V6/V1⁺ 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 V6/V1⁺ T cells. To further investigate the role of V6/V1⁺ T cells in B. subtilis-induced lung fibrosis, we exposed transgenic V6/V1 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 V6/V1⁺ T cells, a compensatory increase in IL-17A expression by CD4⁺ T cells was seen in the absence of T cells that resulted in similar levels of IL-17A in the lungs of TCR^–/– and wild-type C57BL/6 mice. In combination, our data suggest an important role for IL-17A-expressing T lymphocytes, both and β T cells, in eliminating this microorganism that prevents excessive inflammation and eventual lung fibrosis in this murine model of B. subtilis-induced hypersensitivity pneumonitis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work is supported by National Institutes of Health Grants HL62410 and ES011810 (to A.P.F.) and HL89766 (to P.L.S.).

² Address correspondence and reprint requests to Dr. Philip L. Simonian, Divisions of Clinical Immunology and Pulmonary Sciences/Critical Care Medicine, B164, RC2, Room 10005, University of Colorado Denver, 12700 East 19th Avenue, Aurora, CO 80045. E-mail address: philip.simonian{at}ucdenver.edu

³ Abbreviations used in this paper: HP, hypersensitivity pneumonitis; wt, wild type.