Loss of regulatory capacity in Treg cells following rhinovirus infection

• Published in: Journal of allergy and clinical immunology 2021-10, Vol.148 (4), p.1016-1029.e16
• Main Authors: Jansen, Kirstin, Wirz, Oliver F., van de Veen, Willem, Tan, Ge, Mirer, David, Sokolowska, Milena, Satitsuksanoa, Pattraporn, Message, Simon D., Kebadze, Tatiana, Glanville, Nicholas, Mallia, Patrick, Skiepko, Roman, Eljaszewicz, Andrzej, Moniuszko, Marcin, Cardoso, Carlos, Gern, James E., Papadopoulos, Nikolaos G., Akdis, Cezmi A., Johnston, Sebastian L., Nadeau, Kari C., Akdis, Mübeccel
• Format: Article
• Language: English
• Subjects: allergic asthma; antiviral response; experimental infection; interferon-induced genes; proinflammatory cytokines; rhinovirus 16; rhinovirus infection; RV-A16; suppressive capacity; Treg cells
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2021.05.045

Respiratory infections with rhinoviruses (RV) are strongly associated with development and exacerbations of asthma, and they pose an additional health risk for subjects with allergy. How RV infections and chronic allergic diseases are linked and what role RV plays in the breaking of tolerance in regulatory T (Treg) cells is unknown. Therefore, this study aims to investigate the effects of RV on Treg cells. Treg cells were isolated from subjects with asthma and controls after experimental infection with the RV-A16 (RV16) and analyzed with next-generation sequencing. Additionally, suppression assays, quantitative PCR assays, and protein quantifications were performed with Treg cells after in vitro RV16 infection. RV16 induced a strong antiviral response in Treg cells from subjects with asthma and controls, including the upregulation of IFI44L, MX1, ISG15, IRF7, and STAT1. In subjects with asthma, the inflammatory response was exaggerated and showed a dysregulated immune response compared with that in the controls. Furthermore, subjects with asthma failed to upregulate several immunosuppressive molecules such as CTLA4 and CD69, and they upregulated the inflammasome-related genes PYCARD and AIM2. Additionally, RV16 reduced the suppressive capacity of Treg cells from healthy subjects and subjects with asthma in vitro and increased TH2 cell–type cytokine production. Treg cells from healthy subjects and subjects with asthma displayed an antiviral response after RV infection and showed reduced suppressive capacity. These data suggest that Treg cell 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. [Display omitted]