αβ cells and a mixed Th1/Th17 response are important in organic dust-induced airway disease

Background: Organic dust exposure in agricultural environments induces an inflammatory response that attenuates over time, yet repetitive dust exposures result in chronic lung diseases. Animalmodels resembling this chronic lung inflammatory response have been developed, yet the underlying cellular mechanisms are not well defined. Objective: Because mice repetitively exposed to organic dust extracts (DE) display increased CD3 T cell lung infiltrates, we sought to determine the phenotype and importance of these cells. Methods: Mice received swine confinement DE repetitively for 3 weeks by established intranasal inhalation protocol. Studies were conducted with peptidoglycan (PGN) because it is a major DE component in large animal farming environments and has shared similar biologic effects with DE. Enumeration of T cells and intracellular cytokine profiles were conducted by flow cytometry techniques. Whole lung homogenate cytokines were analyzed by multiplex immunoassay. T cell receptor (TCR) knockouts were used to determine the functional importance of -expressing T cells. Results: DE increased lung-associated CD3 CD4 T cells and interleukin (IL)-17 (but not IL-4, interferon [IFN], IL-10) producing CD4 T cells. PGN treatment resulted in increased IL-17 and IFNproducing CD4 T cells and IFNproducing CD8 T cells. Both DE and PGN augmented expression of cytokines associated with Th1 and Th17 polarization in lung homogenates. DE-induced lung mononuclear aggregates and bronchiolar compartment inflammation were significantly reduced in TCR knockout animals; however, neutrophil influx and alveolar compartment inflammation were not affected. Conclusion: Studies demonstrated that DE and PGN exposure promote a Th1/Th17 lung microenvironment and that -expressing T cells are important in mediating DE-induced lung pathologic conditions. 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.