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Rhinovirus infection interferes with induction of tolerance to aeroantigens through OX40 ligand, thymic stromal lymphopoietin, and IL-33.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2016 Jan; Vol. 137 (1), pp. 278-288.e6. Date of Electronic Publication: 2015 Jun 19. - Publication Year :
- 2016
-
Abstract
- Background: Rhinovirus infection at an early age has been associated with development of asthma, but how rhinovirus influences the immune response is not clear.<br />Objective: Tolerance to inhaled antigen is mediated through induction of regulatory T (Treg) cells, and we examined whether rhinovirus infection of the respiratory tract can block airway tolerance by modulating Treg cells.<br />Methods: The immune response to intranasal ovalbumin in mice was assessed with concomitant infection with RV1B, and the factors induced in vivo were compared with those made by human lung epithelial cells infected in vitro with RV16.<br />Results: RV1B infection of mice abrogated tolerance induced by inhalation of soluble ovalbumin, suppressing the normal generation of forkhead box protein 3-positive Treg cells while promoting TH2 cells. Furthermore, RV1B infection led to susceptibility to asthmatic lung disease when mice subsequently re-encountered aeroantigen. RV1B promoted early in vivo expression of the TNF family protein OX40 ligand on lung dendritic cells that was dependent on the innate cytokine thymic stromal lymphopoietin (TSLP) and also induced another innate cytokine, IL-33. Inhibiting each of these pathways allowed the natural development of Treg cells while minimizing TH2 differentiation and restored tolerance in the face of RV1B infection. In accordance, RV16 infection of human lung epithelial cells upregulated TSLP and IL-33 expression.<br />Conclusions: These results suggest that infection of the respiratory epithelium with rhinovirus can antagonize tolerance to inhaled antigen through combined induction of TSLP, IL-33, and OX40 ligand and that this can lead to susceptibility to asthmatic lung inflammation.<br /> (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antigens immunology
Bronchoalveolar Lavage Fluid immunology
Epithelial Cells
Humans
Interleukin-13 immunology
Interleukin-4 immunology
Lung cytology
Mice, Inbred C57BL
Mice, Transgenic
OX40 Ligand
Ovalbumin immunology
Respiratory Hypersensitivity immunology
T-Lymphocytes immunology
Thymic Stromal Lymphopoietin
Cytokines immunology
Immune Tolerance
Interleukin-33 immunology
Membrane Glycoproteins immunology
Picornaviridae Infections immunology
Rhinovirus
Tumor Necrosis Factors immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6825
- Volume :
- 137
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 26100084
- Full Text :
- https://doi.org/10.1016/j.jaci.2015.05.007