Yao, S.Jiang, L.Moser, E. K.Jewett, L. B.Wright, J.Du, J.Zhou, B.Davis, S. D.Krupp, N. L.Braciale, T. J.Sun, J.2016-11-042016-11-042015-12Yao, S., Jiang, L., Moser, E., Jewett, L., Wright, J., Du, J., … Sun, J. (2015). Control of pathogenic effector T-cell activities in situ by PD-L1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection. Mucosal Immunology, 8(4), 746–759. http://doi.org/10.1038/mi.2014.1061935-3456https://hdl.handle.net/1805/11400Respiratory syncytial virus (RSV) infection is a leading cause of severe lower respiratory tract illness in young infants, the elderly and immunocompromised individuals. We demonstrate here that the co-inhibitory molecule programmed cell death 1 (PD-1) is selectively upregulated on T cells within the respiratory tract during both murine and human RSV infection. Importantly, the interaction of PD-1 with its ligand PD-L1 is vital to restrict the pro-inflammatory activities of lung effector T cells in situ, thereby inhibiting the development of excessive pulmonary inflammation and injury during RSV infection. We further identify that PD-L1 expression on lung inflammatory dendritic cells is critical to suppress inflammatory T-cell activities, and an interferon-STAT1-IRF1 axis is responsible for increased PD-L1 expression on lung inflammatory dendritic cells. Our findings suggest a potentially critical role of PD-L1 and PD-1 interactions in the lung for controlling host inflammatory responses and disease progression in clinical RSV infection.en-USPublisher PolicyAntigens, CD274metabolismDendritic CellsimmunologyRespiratory Syncytial Virus InfectionsRespiratory Syncytial VirusesT-Lymphocyte SubsetsArticle