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Loss of regulatory capacity in T regulatory cells upon rhinovirus infection.
Loss of regulatory capacity in T regulatory cells upon rhinovirus infection. The Journal of allergy and clinical immunology Jansen, K., Wirz, O. F., van de Veen, W., Tan, G., Mirer, D., Sokolowska, M., Satitsuksanoa, P., Message, S. D., Kebadze, T., Glanville, N., Mallia, P., Skiepko, R., Eljaszewicz, A., Moniuszko, M., Cardoso, C., Gern, J. E., Papadopoulos, N. G., Akdis, C. A., Johnston, S. L., Nadeau, K. C., Akdis, M. 2021Abstract
Respiratory infections with rhinoviruses (RV) are strongly associated with the development and exacerbations of asthma and pose an additional health risk for allergic subjects.How RV infections and chronic allergic diseases are linked, and which role RV plays in the breaking of tolerance in T regulatory cells (Tregs) is unknown. Therefore this study aims to investigate the effects of RV on Tregs.Tregs were isolated from asthmatic subjects and controls after experimental infection with RV16 and were analyzed with next-generation sequencing. Additionally, suppression assays, qPCRs, and protein quantifications were performed with Tregs after in vitro RV16 infection.RV16 induced a strong antiviral response in Tregs from asthmatic subjects and controls, including the upregulation of IFI44L, MX1, ISG15, IRF7, and STAT1. In asthmatic subjects, the inflammatory response was exaggerated and showed a dysregulated immune response compared to controls. Furthermore, asthmatic subjects failed to upregulate several immunosuppressive molecules such as CTLA4 and CD69 and upregulated the inflammasome related genes PYCARD and AIM2. Additionally, RV16 reduced the suppressive capacity of Tregs of healthy and asthmatic subjects in vitro and increased Th2-type cytokine production.Tregs from healthy and asthmatic subjects displayed an anti-viral response after RV infection and showed reduced suppressive capacity. This data suggest that Treg function might be altered or impaired during RV infections, which might play an important role in the association between RV and the development of asthma and asthma exacerbations.
View details for DOI 10.1016/j.jaci.2021.05.045
View details for PubMedID 34153372