Loss of regulatory capacity in Treg cells following rhinovirus infection

Kirstin Jansen; Oliver F Wirz; Willem van de Veen; Ge Tan; David Mirer; Milena Sokolowska; Pattraporn Satitsuksanoa; Simon D Message; Tatiana Kebadze; Nicholas Glanville; Patrick Mallia; Roman Skiepko; Andrzej Eljaszewicz; Marcin Moniuszko; Carlos Cardoso; James E Gern; Nikolaos G Papadopoulos; Cezmi A Akdis; Sebastian L Johnston; Kari C Nadeau; Mübeccel Akdis

doi:10.1016/j.jaci.2021.05.045

Loss of regulatory capacity in Treg cells following rhinovirus infection

J Allergy Clin Immunol. 2021 Oct;148(4):1016-1029.e16. doi: 10.1016/j.jaci.2021.05.045. Epub 2021 Jun 18.

Authors

Kirstin Jansen¹, Oliver F Wirz¹, Willem van de Veen², Ge Tan³, David Mirer¹, Milena Sokolowska¹, Pattraporn Satitsuksanoa¹, Simon D Message⁴, Tatiana Kebadze⁴, Nicholas Glanville⁴, Patrick Mallia⁴, Roman Skiepko⁵, Andrzej Eljaszewicz⁵, Marcin Moniuszko⁵, Carlos Cardoso⁶, James E Gern⁷, Nikolaos G Papadopoulos⁸, Cezmi A Akdis², Sebastian L Johnston⁴, Kari C Nadeau⁹, Mübeccel Akdis¹⁰

Affiliations

¹ Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland.
² Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland; Christine Kühne Center for Allergy Research and Education, Davos, Switzerland.
³ Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland; Functional Genomics Center Zürich, ETH Zürich/University of Zürich, Zürich, Switzerland.
⁴ National Heart and Lung Institute, Imperial College London, London, United Kingdom.
⁵ Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Białystok, Poland.
⁶ Pneumonology Department, Hochgebirgsklinik Davos, Davos, Switzerland.
⁷ Department of Pediatrics, University of Wisconsin-Madison, Madison, Wis.
⁸ Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, United Kingdom; Allergy Department, Second Pediatric Clinic, University of Athens, Athens, Greece.
⁹ Sean N. Parker Center for Allergy and Asthma Research, Department of Medicine, Stanford University, Palo Alto, Calif.
¹⁰ Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland. Electronic address: akdism@siaf.uzh.ch.

PMID: 34153372
DOI: 10.1016/j.jaci.2021.05.045

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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 T_H2 cell-type cytokine production.

Conclusions: 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.

Keywords: RV-A16; Treg cells; allergic asthma; antiviral response; experimental infection; interferon-induced genes; proinflammatory cytokines; rhinovirus 16; rhinovirus infection; suppressive capacity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Asthma / immunology*
Cytokines / immunology
Female
Humans
Male
Picornaviridae Infections / immunology*
Rhinovirus* / genetics
T-Lymphocytes, Regulatory / immunology*
Young Adult

Substances

Cytokines

Abstract

Publication types

MeSH terms

Substances

Grants and funding