Abstract
γδ T cells function in innate and adaptive immunity and are primed for secondary responses by procyanidin components of unripe apple peel (APP). In this study, we investigate the effects of APP and purified procyanidins on γδ T-cell gene expression. A microarray analysis was performed on bovine γδ T cells treated with APP; increases in transcripts encoding granulocyte-monocyte colony stimulating factor (GM-CSF), IL-8 and IL-17, but not markers of TCR stimulation such as IFNγ, were observed. Key responses were confirmed in human, mouse and bovine cells by reverse transcription-PCR and/or ELISA, indicating a conserved response to procyanidins. In vivo relevance of the cytokine response was shown in mice following intraperitoneal injection of APP, which induced production of CXCL1/KC and resulted in neutrophil influx to the blood and peritoneum. In the human T-cell line, MOLT-14, GM-CSF and IL-8 transcripts were increased and stabilized in cells treated with crude APP or purified procyanidins. The ERK1/2 MAPK pathway was activated in APP-treated cells, and necessary for transcript stabilization. Our data describe a unique γδ T-cell inflammatory response during procyanidin treatment and suggest that transcript stability mechanisms could account, at least in part, for the priming phenotype.
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Acknowledgements
Dr Ed Schmidt and Kate McInnerney (Montana State University) are acknowledged for critical review of the manuscript and technical assistance with microarray experiments, respectively.
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MAJ holds shares in LigoCyte Pharmaceuticals, Inc, which together with Montana State University held a National Institutes of Health contract that partially funded this work. All other authors have no financial conflict of interest.
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This study was supported by funding from the National Institutes of Health (NIH) (NCCAM AT0004986-01), NIAID Contract (HHSN26620040009C/N01-AI-40009), NIH COBRE, and support from the Murdock Charitable Trust.
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Daughenbaugh, K., Holderness, J., Graff, J. et al. Contribution of transcript stability to a conserved procyanidin-induced cytokine response in γδ T cells. Genes Immun 12, 378–389 (2011). https://doi.org/10.1038/gene.2011.7
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DOI: https://doi.org/10.1038/gene.2011.7
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