IL-17 Producing γδ T Cells are Required for a Controlled Inflammatory Response after Bleomycin-induced Lung Injury
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γδ T cells play a key role in the regulation of inflammatory responses in epithelial tissue, and in adaptive immunity, as γδ T cell deficient mice have a severely impaired capacity to clear lung pathogens. γδ T cells regulate the initial inflammatory response to microbial invasion and thereby protect against tissue injury. Here we examined the response of γδ T cells to lung injury induced by bleomycin, in an effort to study the inflammatory response in the absence of any adaptive immune response to a pathogen.
After lung injury by bleomycin, we localized the γδ T cells to the lung lesions. γδ T cells were the predominant source of IL-17 (as detected by flow cytometry and real-time PCR). Moreover, γδ T cell knockout mice showed a significant reduction in cellular infiltration into the airways, reduced expression of IL-6 in the lung, and a significant delay in epithelial repair.
Mouse γδ T cells produce IL-17 in response to lung injury and are required for an organized inflammatory response and epithelial repair. The lack of γδ T cells correlates with increased inflammation and fibrosis.
Key wordsγδ T cell bleomycin lung fibrosis IL-17
We acknowledge the help of Kathy Schell and Patricia Simms for the cell sorting. This research was supported by a grant from the NHLBI–NIH # RO1 HL 56262 and by a grant from the Department of Surgery, Loyola University of Chicago.
RKB designed the study, carried out the flow cytometry studies, participated in the bleomycin instillation, drafted the manuscript, and performed the statistical analysis.
CF performed the staining of the tissue sections and helped with the bleomycin instillation. PN carried out the molecular analysis of the IL-17 expression. MS participated in the flow cytometry studies and the bleomycin instillation. ASK carried out the pathology analysis of the mouse lungs. MK participated in the preparation of the mouse lungs and the pathology analysis. LP carried out the confocal microscopy. DAF participated in the design of the study and helped to draft the manuscript. DMH performed the morphometric analysis of the epithelial repair. RBL participated in the design of the study and helped to draft the manuscript.
The authors declare that they have no competing interests.
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